The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.
A barbiturate that is effective as a hypnotic and sedative.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Dynamic and kinetic mechanisms of exogenous chemical and DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology.
The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.
A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29)
A genus of zygomycetous fungi of the family Cunninghamellaceae, order MUCORALES. Some species cause systemic infections in humans.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.
The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.
A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.
A cytochrome P450 enzyme that catalyzes the hydroxylation of many drugs and environmental chemicals, such as DEBRISOQUINE; ADRENERGIC RECEPTOR ANTAGONISTS; and TRICYCLIC ANTIDEPRESSANTS. This enzyme is deficient in up to 10 percent of the Caucasian population.
Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.
7-Hydroxycoumarins. Substances present in many plants, especially umbelliferae. Umbelliferones are used in sunscreen preparations and may be mutagenic. Their derivatives are used in liver therapy, as reagents, plant growth factors, sunscreens, insecticides, parasiticides, choleretics, spasmolytics, etc.
The chemical reactions involved in the production and utilization of various forms of energy in cells.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Glycosides of GLUCURONIC ACID formed by the reaction of URIDINE DIPHOSPHATE GLUCURONIC ACID with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and BILIRUBIN metabolism to a more water-soluble compound that can be eliminated in the URINE and BILE.
An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.
A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.
An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.
A liver microsomal cytochrome P450 enzyme that catalyzes the 16-alpha-hydroxylation of a broad spectrum of steroids, fatty acids, and xenobiotics in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme is encoded by a number of genes from several CYP2 subfamilies.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.
The rate dynamics in chemical or physical systems.
A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).
Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A drug-metabolizing enzyme found in the hepatic, placental and intestinal microsomes that metabolizes 7-alkoxycoumarin to 7-hydroxycoumarin. The enzyme is cytochrome P-450- dependent.
A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC
Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
Carboxylesterase is a serine-dependent esterase with wide substrate specificity. The enzyme is involved in the detoxification of XENOBIOTICS and the activation of ester and of amide PRODRUGS.
Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.
Chromatographic techniques in which the mobile phase is a liquid.
Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.
The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.
The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
A pyrazolone with analgesic, anti-inflammatory, and antipyretic properties but has risk of AGRANULOCYTOSIS. A breath test with 13C-labeled aminopyrine has been used as a non-invasive measure of CYTOCHROME P-450 metabolic activity in LIVER FUNCTION TESTS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Methyl analog of DEXTRORPHAN that shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is an NMDA receptor antagonist (RECEPTORS, N-METHYL-D-ASPARTATE) and acts as a non-competitive channel blocker. It is one of the widely used ANTITUSSIVES, and is also used to study the involvement of glutamate receptors in neurotoxicity.
A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).
An enzyme that catalyzes the transfer of acetyl groups from ACETYL-COA to arylamines. It can also catalyze acetyl transfer between arylamines without COENZYME A and has a wide specificity for aromatic amines, including SEROTONIN. However, arylamine N-acetyltransferase should not be confused with the enzyme ARYLALKYLAMINE N-ACETYLTRANSFERASE which is also referred to as SEROTONIN ACETYLTRANSFERASE.
A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)
Cytochromes of the b group that are found bound to cytoplasmic side of ENDOPLASMIC RETICULUM. They serve as electron carrier proteins for a variety of membrane-bound OXYGENASES. They are reduced by the enzyme CYTOCHROME-B(5) REDUCTASE.
A drug-metabolizing, cytochrome P-450 enzyme which catalyzes the hydroxylation of aniline to hydroxyaniline in the presence of reduced flavoprotein and molecular oxygen. EC 1.14.14.-.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.
A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.
A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
A carcinogen that is often used in experimental cancer studies.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A mass spectrometry technique using two (MS/MS) or more mass analyzers. With two in tandem, the precursor ions are mass-selected by a first mass analyzer, and focused into a collision region where they are then fragmented into product ions which are then characterized by a second mass analyzer. A variety of techniques are used to separate the compounds, ionize them, and introduce them to the first mass analyzer. For example, for in GC-MS/MS, GAS CHROMATOGRAPHY-MASS SPECTROMETRY is involved in separating relatively small compounds by GAS CHROMATOGRAPHY prior to injecting them into an ionization chamber for the mass selection.
Chlorinated ethanes which are used extensively as industrial solvents. They have been utilized in numerous home-use products including spot remover preparations and inhalant decongestant sprays. These compounds cause central nervous system and cardiovascular depression and are hepatotoxic. Include 1,1,1- and 1,1,2-isomers.
An emulsifying agent produced in the LIVER and secreted into the DUODENUM. Its composition includes BILE ACIDS AND SALTS; CHOLESTEROL; and ELECTROLYTES. It aids DIGESTION of fats in the duodenum.
Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.
Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure.
The giving of drugs, chemicals, or other substances by mouth.
Removal of a drug from the market due to the identification of an intrinsic property of the drug that results in a serious risk to public health.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
The relationship between the dose of an administered drug and the response of the organism to the drug.
The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.
A major cytochrome P-450 enzyme which is inducible by PHENOBARBITAL in both the LIVER and SMALL INTESTINE. It is active in the metabolism of compounds like pentoxyresorufin, TESTOSTERONE, and ANDROSTENEDIONE. This enzyme, encoded by CYP2B1 gene, also mediates the activation of CYCLOPHOSPHAMIDE and IFOSFAMIDE to MUTAGENS.
Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.
A drug-metabolizing enzyme of the hepatic microsomal oxidase system which catalyzes the oxidation of the N-methyl group of ethylmorphine with the formation of formaldehyde.
The chemical reactions that occur within the cells, tissues, or an organism. These processes include both the biosynthesis (ANABOLISM) and the breakdown (CATABOLISM) of organic materials utilized by the living organism.
The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.
Elements of limited time intervals, contributing to particular results or situations.
A member of the BENZODIOXOLES that is a constituent of several VOLATILE OILS, notably SASSAFRAS oil. It is a precursor in the synthesis of the insecticide PIPERONYL BUTOXIDE and the drug N-methyl-3,4-methylenedioxyamphetamine (MDMA).
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, and chemicals from the environment.
Enzymes which transfer sulfate groups to various acceptor molecules. They are involved in posttranslational sulfation of proteins and sulfate conjugation of exogenous chemicals and bile acids. EC 2.8.2.
A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.
Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.
A benzodiazepine derivative used as an anticonvulsant and hypnotic.
A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.
A 2,4,6-trinitrotoluene, which is an explosive chemical that can cause skin irritation and other toxic consequences.
A quinazoline derivative with hypnotic and sedative properties. It has been withdrawn from the market in many countries because of problems with abuse. (From Martindale, The Extra Pharmacopoeia, 30th ed, p604)
Proteins prepared by recombinant DNA technology.
Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.
A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A sulfotransferase that catalyzes the sulfation of a phenol in the presence of 3'-phosphoadenylylsulfate as sulfate donor to yield an aryl sulfate and adenosine 3',5'-bisphosphate. A number of aromatic compounds can act as acceptors; however, organic hydroxylamines are not substrates. Sulfate conjugation by this enzyme is a major pathway for the biotransformation of phenolic and catechol drugs as well as neurotransmitters. EC
The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)
Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.
Uptake of substances through the lining of the INTESTINES.
A barbiturate with hypnotic and sedative properties (but not antianxiety). Adverse effects are mainly a consequence of dose-related CNS depression and the risk of dependence with continued use is high. (From Martindale, The Extra Pharmacopoeia, 30th ed, p565)
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)
Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.
Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
OXADIAZOLES bearing an oxygen at the 5-position. They are mesoionic, with delocalized positive and negative charges.
An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.
Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water.
A macrolide antibiotic that is similar to ERYTHROMYCIN.
Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)
A skin irritant that may cause dermatitis of both primary and allergic types. Contact sensitization with DNCB has been used as a measure of cellular immunity. DNCB is also used as a reagent for the detection and determination of pyridine compounds.
A selective triazine herbicide. Inhalation hazard is low and there are no apparent skin manifestations or other toxicity in humans. Acutely poisoned sheep and cattle may show muscular spasms, fasciculations, stiff gait, increased respiratory rates, adrenal degeneration, and congestion of the lungs, liver, and kidneys. (From The Merck Index, 11th ed)
A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds.
A genus of gram-positive BACTERIA in the family Gordoniaceae, isolated from soil and from sputa of patients with chest disorders. It is also used for biotransformation of natural products.
Heterocyclic rings containing three nitrogen atoms, commonly in 1,2,4 or 1,3,5 or 2,4,6 formats. Some are used as HERBICIDES.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.
An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992)
Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.
Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc.
A butyl-diphenyl-pyrazolidinedione that has anti-inflammatory, antipyretic, and analgesic activities. It has been used in ANKYLOSING SPONDYLITIS; RHEUMATOID ARTHRITIS; and REACTIVE ARTHRITIS.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.
A quinolizidine alkaloid isolated from several FABACEAE including LUPINUS; SPARTIUM; and CYTISUS. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest as an indicator of CYP2D6 genotype.
A colorless to white crystalline compound with a camphoraceous odor and taste. It is a widely used preservative in various pharmaceutical solutions, especially injectables. Also, it is an active ingredient in certain oral sedatives and topical anesthetics.
The portion of the GASTROINTESTINAL TRACT between the PYLORUS of the STOMACH and the ILEOCECAL VALVE of the LARGE INTESTINE. It is divisible into three portions: the DUODENUM, the JEJUNUM, and the ILEUM.
Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.
Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.
Established cell cultures that have the potential to propagate indefinitely.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
An anadromous species of SALMON ranging from the Arctic and Pacific Oceans to Monterey Bay, California and inhabiting ocean and coastal streams. It is familiarly known as the coho or silver salmon. It is relatively small but its light-colored flesh is of good flavor.
An inhalation anesthetic. Currently, methoxyflurane is rarely used for surgical, obstetric, or dental anesthesia. If so employed, it should be administered with NITROUS OXIDE to achieve a relatively light level of anesthesia, and a neuromuscular blocking agent given concurrently to obtain the desired degree of muscular relaxation. (From AMA Drug Evaluations Annual, 1994, p180)
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A widely used industrial solvent.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The science concerned with the detection, chemical composition, and biological action of toxic substances or poisons and the treatment and prevention of toxic manifestations.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
A non-steroidal ESTROGEN generated when soybean products are metabolized by certain bacteria in the intestines.
An organophosphorus compound isolated from human and animal tissues.
A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.
Non-steroidal compounds with estrogenic activity.
An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.
Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.
Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.
Societies whose membership is limited to pharmacists.
A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.
A centrally acting central muscle relaxant with sedative properties. It is claimed to inhibit muscle spasm by exerting an effect primarily at the level of the spinal cord and subcortical areas of the brain. (From Martindale, The Extra Pharmacopoea, 30th ed, p1202)
Compounds with a core of 10 carbons generally formed via the mevalonate pathway from the combination of 3,3-dimethylallyl pyrophosphate and isopentenyl pyrophosphate. They are cyclized and oxidized in a variety of ways. Due to the low molecular weight many of them exist in the form of essential oils (OILS, VOLATILE).
An array of tests used to determine the toxicity of a substance to living systems. These include tests on clinical drugs, foods, and environmental pollutants.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
Nicotinamide adenine dinucleotide phosphate. A coenzyme composed of ribosylnicotinamide 5'-phosphate (NMN) coupled by pyrophosphate linkage to the 5'-phosphate adenosine 2',5'-bisphosphate. It serves as an electron carrier in a number of reactions, being alternately oxidized (NADP+) and reduced (NADPH). (Dorland, 27th ed)
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.
Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.
A catatoxic steroid and microsomal enzyme inducer having significant effects on the induction of cytochrome P450. It has also demonstrated the potential for protective capability against acetaminophen-induced liver damage.
Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.
Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.
A major group of unsaturated cyclic hydrocarbons containing two or more rings. The vast number of compounds of this important group, derived chiefly from petroleum and coal tar, are rather highly reactive and chemically versatile. The name is due to the strong and not unpleasant odor characteristic of most substances of this nature. (From Hawley's Condensed Chemical Dictionary, 12th ed, p96)
A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.
Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Colorless reduced precursors of porphyrins in which the pyrrole rings are linked by methylene (-CH2-) bridges.
A cell line derived from cultured tumor cells.
A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.
A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)
A flavanone glycoside found in CITRUS fruit peels.
The metabolism of a drug or toxin in a body is an example of a biotransformation. The body typically deals with a foreign ... Biotransformation of xenobiotics can dominate toxicokinetics and the metabolites may reach higher concentrations in organisms ... phase І phase II Drugs can undergo one of four potential biotransformations: Active Drug to Inactive Metabolite, Active Drug to ... Biotransformation of Drugs Biodegradation, Bioremediation and Biotransformation Microbial Biodegradation Biotransformation and ...
Bioremediation and Biotransformation History History of Xenobiotic Metabolism at the Wayback Machine (archived July 13, 2007) ... of Minnesota Biocatalysis/Biodegradation Database SPORCalc Drug metabolism Small Molecule Drug Metabolism Drug metabolism ... For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. Drug metabolism ... The study of drug metabolism is called pharmacokinetics. The metabolism of pharmaceutical drugs is an important aspect of ...
... drug metabolism by microbial enzymes modifying the drug's pharmacokinetic profile, and microbial drug metabolism affecting a ... a wealth of literature has long been available about the biotransformation of xenobiotics, notably by gut bacteria (reviewed in ... More than 30 drugs have been shown to be metabolized by gut microbiota. The microbial metabolism of drugs can sometimes ... Apart from carbohydrates, gut microbiota can also metabolize other xenobiotics such as drugs, phytochemicals, and food ...
Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes ... Galvão TC, Mohn WW, de Lorenzo V (October 2005). "Exploring the microbial biodegradation and biotransformation gene pool". ... evolution and drug metabolism in humans". Current Drug Metabolism. 3 (6): 561-97. doi:10.2174/1389200023337054. PMID 12369887. ... production Stream metabolism Sulfur metabolism Thermic effect of food Urban metabolism Water metabolism Overflow metabolism ...
NAT2 is involved in the metabolism of xenobiotics, which can lead to both the inactivation of drugs and formation of toxic ... The biotransformation of xenobiotics may occur in three phases. In phase I, reactive and polar groups are introduced into the ... phase II metabolism). This is especially important in the metabolism and excretion of drug products (drug metabolism). NAT ... Each individual metabolizes xenobiotics at different rates, resulting from polymorphisms of the xenobiotic metabolism genes. ...
Basic Principles and Its Use as a Tool in Drug Metabolism". Ур.: Horning MG, Mitchell J. Drug metabolism and drug toxicity. New ... Galvão T, Mohn W, de Lorenzo V (2005). "Exploring the microbial biodegradation and biotransformation gene pool". Trends ... Janssen D, Dinkla I, Poelarends G, Terpstra P (2005). "Bacterial degradation of xenobiotic compounds: evolution and ... Basic Principles and Its Use as a Tool in Drug Metabolism". Ур.: Horning MG, Mitchell J. Drug metabolism and drug toxicity. New ...
Also, scarcities have been seen to alter the metabolism of certain drugs and xenobiotics in mice. Most importantly, researchers ... Another function of the GSTZ1 is that it is in control of the biotransformation of alpha-haloacids, like dichloroacetic acid ( ... Drug Metabolism and Disposition. 40 (2): 232-9. doi:10.1124/dmd.111.041533. PMC 3263939. PMID 22028318. Ketterer B (Oct 2001 ... It is the only enzyme in the GST family that catalyses a significant process in intermediary metabolism and it ensures that ...
It is among the reactions in phase II drug metabolism, frequently effective in rendering a xenobiotic less active from a ... This biotransformation involves a sulfotransferase enzyme catalyzing the transfer of a sulfo group from a donor cosubstrate, ... pharmacological and toxicological standpoint, but sometimes playing a role in the activation of xenobiotics (e.g. aromatic ...
... metabolism and elimination. At a practical level, a drug's bioavailability can be defined as the proportion of the drug that ... Metabolism (or biotransformation, or inactivation) - the recognition by the organism that a foreign substance is present and ... The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics ... metabolism + excretion of the drugs. The resulting decrease of the drug's plasma concentration follows a biphasic pattern (see ...
Danielson P (2002). "The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans". Curr Drug Metab. ... Galvão T, Mohn W, de Lorenzo V (2005). "Exploring the microbial biodegradation and biotransformation gene pool". Trends ... Janssen D, Dinkla I, Poelarends G, Terpstra P (2005). "Bacterial degradation of xenobiotic compounds: evolution and ... Testa B, Krämer S (2006). "The biochemistry of drug metabolism-an introduction: part 1. Principles and overview". Chem ...
... and antibacterial drug resistance. GSTs also have important roles in metabolism, such as signaling-ligand biosynthesis, ... Xenobiotics are compounds foreign to the bacterium's natural biochemistry, and phase II of their detoxification involves ... Bacterial GSTs are involved in a variety of distinct processes such as biotransformation of toxic compounds, protection against ... transferases is to reduce the toxic effects of xenobiotics from the cell using the phase II system of detoxification metabolism ...
Lack of prediction by the erythromycin breath test". Drug Metabolism and Disposition. 22 (6): 947-55. PMID 7895614. Schuetz JD ... is one of the most versatile of the biotransformation systems that facilitate the elimination of drugs (37% of the 200 most ... It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Immunoblot ... Drug Metabolism and Disposition. 24 (8): 899-905. PMID 8869826. Kivistö KT, Bookjans G, Fromm MF, Griese EU, Münzel P, Kroemer ...
Drug metabolism. CYPs are the major enzymes involved in drug metabolism, accounting for about 75% of the total metabolism.[17] ... Those so far identified are generally involved in either biotransformation of xenobiotic compounds (e.g. CYP105A1 from ... For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body ... evolution and drug metabolism in humans". Current Drug Metabolism. 3 (6): 561-97. doi:10.2174/1389200023337054. PMID 12369887. ...
One of the major fields within pharmaceutical bioinformatics is the in silico metabolism prediction of drug candidates. This ... to understand how xenobiotics interact with the human body and the drug discovery process. Whereas traditional bioinformatics ... "Use of historic metabolic biotransformation data as a means of anticipating metabolic sites using MetaPrint2D and Bioclipse". ... A 2D Method for Prediction of Cytochrome P450-Mediated Drug Metabolism". ACS Medicinal Chemistry Letters. 1 (3): 96-100. doi: ...
Even though pharmacomicrobiomics is often interpreted as the impact the microbiome has on xenobiotic metabolism, the term can ... "The gastrointestinal microbiota as a site for the biotransformation of drugs". Int J Pharm. 363 (1-2): 1-25. doi:10.1016/j. ... Even though most drugs are absorbed in the upper part of the large intestine, long-acting drugs that are exposed to the microbe ... Haiser, HJ; Turnbaugh, PJ (2013). "Developing a metagenomic view of xenobiotic metabolism". Pharmacol. Res. 69 (1): 21-31. doi: ...
... is a microbial model of mammalian drug metabolism. The use of this fungus could reduce the over-all need ... Wackett, L. P.; Gibson, D. T. (1982). "Metabolism of xenobiotic compounds by enzymes in cell extracts of the fungus ... Moody, J. D.; Freeman, J. P.; Cerniglia, C. E. (1999). "Biotransformation of doxepin by Cunninghamella elegans". Drug ... Asha S, Vidyavathi M (2009). "Cunninghamella - a microbial model for drug metabolism studies - a review". Biotechnol. Adv. 27 ( ...
Carbon monoxide releasing materials (CORMAs) are essentially novel drug formulations and drug delivery platforms which have ... and xenobiotics. The average carboxyhemoglobin (CO-Hb) level in a non-smoker is between 0.2% and 0.85% CO-Hb (whereas a smoker ... have been deployed to induce heme oxygenase and subsequently undergo biotransformation to liberate CO, the inorganic ion, and ... chloride was the first organic CORM orally administered based on previous reports of carboxyhemoglobin formation via metabolism ...
Drug metabolism is usually divided into two phases: phase 1 and phase 2. Phase 1 reaction is thought to prepare a drug for ... The human body identifies almost all drugs as foreign substances (i.e. xenobiotics) and subjects them to various chemical ... 3. Competitive inhibition: Some drugs may share the same P-450 specificity and thus competitively block their bio ... for the variation in drug metabolism between individuals. Genetic variations (polymorphism) in P-450 metabolism should be ...
160-. ISBN 978-0-471-95052-3. Pavel Anzenbacher; Ulrich M. Zanger (23 February 2012). Metabolism of Drugs and Other Xenobiotics ... CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers". Pharmacogenetics. 12 (7): 571-80. doi: ... Poor and intermediate metabolizers have reduced metabolism of the drug as compared to extensive metabolizers; patients with ... Its metabolism is highly stereoselective. Based on in vitro research, the major enzymes involved in the metabolism of doxepin ...
... which is involved in the metabolism of xenobiotics. the concentration of hexobarbital also plays a role in oxygenase and ... This biotransformation step takes place via an epoxide-diol mechanism. The formation of an reactive epoxide, leads to the ... Vermeulen NP, Rietveld CT, Breimer DD (April 1983). "Disposition of hexobarbitone in healthy man: kinetics of parent drug and ... Takenoshita R, Toki S (December 2004). "[New aspects of hexobarbital metabolism: stereoselective metabolism, new metabolic ...
... drug metabolism by microbial enzymes modifying the drug's pharmacokinetic profile, and microbial drug metabolism affecting a ... a wealth of literature has long been available about the biotransformation of xenobiotics, notably by gut bacteria (reviewed in ... "National Drug Code Amphetamine Search Results". National Drug Code Directory. United States Food and Drug Administration. ... In other nations, such as Canada (schedule I drug), the Netherlands (List I drug), the United States (schedule II drug), ...
... drug metabolism by microbial enzymes modifying the drug's pharmacokinetic profile, and microbial drug metabolism affecting a ... a wealth of literature has long been available about the biotransformation of xenobiotics, notably by gut bacteria (reviewed in ... "National Drug Code Amphetamine Search Results". National Drug Code Directory. United States Food and Drug Administration. ... N-containing drugs and xenobiotics oxygenated by FMO "Mydayis Prescribing Information" (PDF). United States Food and Drug ...
Decker M, Arand M, Cronin A (2009). "Mammalian epoxide hydrolases in xenobiotic metabolism and signalling" (PDF). Arch. Toxicol ... Role of EPHX1 expression in pathogenesis of neurodegeneration as Alzheimer´s disease, methamphetamine-induced drug dependence, ... "Genetic polymorphisms of biotransformation enzymes in patients with Hodgkin's and non-Hodgkin's lymphomas". Hum. Mol. Genet. 10 ... relevance to xenobiotic metabolism and toxicity". Crit. Rev. Toxicol. 29 (1): 59-124. doi:10.1080/10408449991349186. PMID ...
Drug metabolism of phenolic drugs, such as paracetamol and salicylamide, is greatly dependent on the phenol sulfoconjugation by ... is important for the detoxification of phenol-containing xenobiotics or endogenous compounds, including the biotransformation ... Levy G (July 1986). "Sulfate conjugation in drug metabolism: role of inorganic sulfate". Federation Proceedings. 45 (8): 2235- ... Drug Metabolism and Disposition. 41 (9): 1642-50. doi:10.1124/dmd.113.050930. PMC 3876809. PMID 23775849. Yeo M, Na YM, Kim DK ...
... metabolism + excretion of the drugs. The resulting decrease of the drug's plasma concentration follows a biphasic pattern (see ... Metabolism that is inactivation of the xenobiotic substance, and finally. *Excretion or elimination of the substance or the ... Pharmacokinetics: 1) Process of the uptake of drugs by the body, the biotransformation they undergo, the distribution of the ... The systemically available fraction of a drug.. 0.8. f. {\displaystyle f}. =. A. U. C. po. ⋅. D. iv. A. U. C. iv. ⋅. D. po. {\ ...
... metabolism in humans is also the target of cholesterol-lowering drugs, such as statins. In humans and other animals the ... Kliewer SA, Goodwin B, Willson TM (Oct 2002). "The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism". ... These modifications are performed using conventional organic synthesis and/or biotransformation techniques. The semisynthesis ... "Human Fungal Pathogens and Drug Resistance Against Azole Drugs". In Arora C, Sajid A, Kalia V (eds.). Drug Resistance in ...
The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as ... Gu J, Su T, Chen Y, Zhang QY, Ding X (Jun 2000). "Expression of biotransformation enzymes in human fetal olfactory mucosa: ... "Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole". Drug Metabolism and ... Drug Metabolism Reviews. 31 (1): 205-34. doi:10.1081/DMR-100101915. PMID 10065373. Capdevila JH, Falck JR, Harris RC (Feb 2000 ...
Drug Metabolism and Drug Interactions. 29 (4): 249-59. doi:10.1515/dmdi-2014-0014. PMC 4407688. PMID 24807167. Annaert P, Ye ZW ... transporting compounds into the hepatocyte for biotransformation. A number of drug-drug interactions have been associated with ... drugs, toxins and other xenobiotics. One family member, OATP2B1, has been shown to use cytoplasmic glutamate as the exchanging ... Drug Metabolism and Drug Interactions. 29 (3): 179-90. doi:10.1515/dmdi-2013-0062. PMC 4407685. PMID 24643910. Khurana V, ...
"Significance of Xenobiotic Metabolism for Bioaccumulation Kinetics of Organic Chemicals in Gammarus pulex". Environmental ... Biotransformation can strongly modify bioaccumulation of chemicals in an organism.[6] ... Drug accumulation ratio. *Environmental impact of pesticides. *International POPs Elimination Network. *Persistent organic ...
PCBs undergo xenobiotic biotransformation, a mechanism used to make lipophilic toxins more polar and more easily excreted from ... Temperature plays a key role in the ecology, physiology and metabolism of aquatic species. The rate of PCB metabolism was ... "Nearly a Decade After Spill, Cleanup of Toxic Site Drags On With PM-Rusted Legacy II". AP NEWS. Retrieved 2020-02-19. " ... The biotransformation is dependent on the number of chlorine atoms present, along with their position on the rings. Phase I ...
Drug Metabolism and Biotransformation XenoBiotic Laboratories. USA. Tel: 352-283-4918. Biography Research Interest Network ... Division of Pharmacokinetics and Metabolism. Central Drug Research Institute. India. Central Drug Research Institute Biography ... Food and Drug Administration (FDA)/Center for Drug Evaluation and Research (CDER). USA ... Department of Chemical Drugs. Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences. Czech Republic ...
Drug Metabolism Reviews: Biotransformation and Disposition of Xenobiotics, 2003; 35(2):179.. Presentations. Palmquist K, ... 12th North American Meeting of the International Society for the Study of Xenobiotics, Providence, RI, October 12-16, 2003.. ...
1996) Biotransformation of xenobiotics. in Casarett and Doulls Toxicology: the Basic Science of Poisons, ed Klaassen CD ( ... in COST B1 Conference on Variability and Specificity in Drug Metabolism, eds Alván G, Balant LP, Bechtel PR, Boobis AR, Gram LF ... in COST B1 Conference on Variability and Specificity in Drug Metabolism, eds Alván G, Balant LP, Bechtel PR, Boobis AR, Gram LF ... Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23: ...
Metabolism of xenobiotics. *Effect of biotransformation on biochemical and pharmacological aspects of drugs ... Role of cytochrome P450 system and other biotransformation enzymes in metabolism of xenobiotics ... Study of metabolism of TKIs by enzymes of 1. phase of biotransformation ... Nanoforms of drugs. *Preparation and characterisation of anticancer drugs in form nanoparticles ...
... is an official online journal of the Japanese Society for the Study of Xenobiotics (JSSX), and it... ... Drug metabolism / Biotransformation. - Pharmacokinetics and pharmacodynamics. - Toxicokinetics and toxicodynamics. - Drug-drug ... Drug Metabolism and Pharmacokinetics (DMPK) is an official online journal of the Japanese Society for the Study of Xenobiotics ... Drug Metabolism and Pharmacokinetics (DMPK) is an official online journal of the Japanese Society for the Study of Xenobiotics ...
Corning provides cryopreserved primary human hepatocytes to support major applications in drug and xenobiotic biotransformation ... One Proven Brand, from Metabolism Studies Through Pre-clinical Drug Development. Enhance the results of your research with ... Performing Drug-Drug Interaction Studies Performing Drug-Drug Interaction Studies This protocol describes the procedure to ... Support ADME assays such as drug metabolism, induction, transporter, and toxicity studies. ...
... and regulatory aspects of oxidative drug metabolizing enzymes. Mainly cytochrome P450-dependent and flavin-containing ... Problems Associated with Assessment of the Contribution of Individual Forms of Cytochrome P450 to the Metabolism of Xenobiotics ... Developmental Regulation of Biotransformation of Drugs and other Xenobiotics Wolfgang Klinger. Pages 237-248 ... Oxidation biology carcinogenesis cell cell culture cytochrome P450 drug enzyme enzymes metabolism molecular biology mutagen ...
... and metabolism of drugs and other xenobiotics. Most of the knowledge regarding the differential hepatic metabolism is based on ... Klinger W. Biotransformation of drugs and other xenobiotics during postnatal development. Exp Toxicol Pathol.1996;48(suppl 1) : ... Developmental changes in xenobiotic metabolism add to the complexity of hepatotoxicity as a result of drugs and environmental ... The ontogenic (developmental) changes in metabolism interact with the genetic determinants of drug metabolism (pharmacogenetics ...
... variability in response to drugs and xenobiotics is related to genetically-determined impairment in drug metabolism. Several ... Tumoral Drug Metabolism: Perspectives and Therapeutic Implications. M.M. Doherty; M. Michael // Current Drug Metabolism;Apr2003 ... Current Drug Metabolism;Mar2009, Vol. 10 Issue 3, p220 It is widely appreciated that as a xenobiotic travels through an ... approach and its application to studies of biotransformation enzymes and drug metabolism is given. Theoretical methods to ...
The metabolism of a drug or toxin in a body is an example of a biotransformation. The body typically deals with a foreign ... Biotransformation of xenobiotics can dominate toxicokinetics and the metabolites may reach higher concentrations in organisms ... phase І phase II Drugs can undergo one of four potential biotransformations: Active Drug to Inactive Metabolite, Active Drug to ... Biotransformation of Drugs Biodegradation, Bioremediation and Biotransformation Microbial Biodegradation Biotransformation and ...
Xenobiotics .39 Metapathway biotransformation .36 2. Drug metabolism - cytochrome P450. Chemical carcinogenesis ... This gene encodes a member of the cytochrome P450 superfamily of enzymes, which participate in drug metabolism and the ... 179) Drugs for CYP3A7 Gene - From: DrugBank, ApexBio, DGIdb, FDA Approved Drugs, HMDB, and Novoseek. ... Among its related pathways are Metabolism and Cytochrome P450 - arranged by substrate type. GO annotations related to this gene ...
Study on structure-function relationships of cytochromes P450 - key enzymes involved in metabolism of drugs and activation of ... Faculty / Chemistry / Department of Biochemistry / Hodek Petr / Modulation of key biotransformation enzymes by xenobiotics ... Role of intestinal microbiota in drug and carcinogen metabolism. *Interaction of selected cosmetic additives with ... Drug. Metab., 15, 829-840 (2014). STIBOROVA, M., LEVOVA, K., BARTA, F., DRACINSKA, H., SULC, M., HODEK, P., FREI, E., ARLT, V. ...
1993) Rat hepatocyte cultures and co-cultures in biotransformation studies of xenobiotics. Toxicology 82:193-208. ... 1989) Disposition, metabolism, and excretion of U-71038, a novel renin inhibitor peptide, in the rat. Drug Metab Dispos 17:518- ... 1994) Kidney and liver contributions to salicylate metabolism in rats. Eur J Drug Metab Pharmacokinet 19:21-26. ... Comparison of the maintenance of mixed function oxidase and conjugation pathways of drug metabolism. Biochem Pharmacol 42:373- ...
... constitute a superfamily of hemoprotein enzymes that are responsible for the biotransformation of numerous xenobiotics, ... Human drug metabolism and the cytochromes P450: application and relevance of in vitro models J Clin Pharmacol. 2001 Nov;41(11): ... drug toxicity, and drug interactions. This review evaluates the major human hepatic drug-metabolizing CYP enzymes and their ... constitute a superfamily of hemoprotein enzymes that are responsible for the biotransformation of numerous xenobiotics, ...
... it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or ... The metabolism of drugs is often divided into two phases, biotransformation and bioconjugation, respectively. The ... One aspect of human metabolism is the excretion of xenobiotics-e.g., drugs or carcinogens-by biochemical transformations. In ... the metabolism of drug candidates is evaluated by in vitro biotransformations (with microsomes or recombinant enzymes), which ...
Chronic inflammation blocks xenobiotic and drug metabolism via inhibition of PXR(1). ... Laymans breakdown: PXR helps dispose of a number of ... Xenobiotic-A substance foreign to the body (BPA, pesticides, herbal supplements, pharmaceutical drugs) ... We know so much about this process because PXR regulates the metabolism of pharmaceutical drugs. PXR regulates their absorption ...
Phase 1 Drug Metabolism (Enzymes, Substrates, and Antibodies) Drug Conjugate Analysis (Enzymes, Substrates and Inhibitors, and ... and excretedthe ADME concept-to optimize drug efficacy. Small molecule organic drugs are considered xenobiotics-compounds ... Biotransformation is also utilized in the metabolism of many prodrugs to their active form, for example enalapril to ... Phase 1 Drug Metabolism: Enzymes, Substrates, and Antibodies *Drug Conjugate Analysis: Enzymes, Substrates and Inhibitors, and ...
VP, Head of Bioanalytical & Acting Head of Drug Metabolism / Biotransformation, XenoBiotic Laboratories, Inc, Plainsboro, NJ. ... Metabolomics in Drug Discovery: Lessons Learned and Path Forward. Petia Shipkova, Bristol-Myers Squibb ... Modern bioanalytical chemists are charged with the task of developing high sensitivity assays for drug candidates with low ...
Phenylalanine 4-monooxygenase and the role of endobiotic metabolism enzymes in xenobiotic biotransformation. Expert Opin Drug ... Parthasarathy A, Cross PJ, Dobson RCJ, Adams LE, Savka MA, Hudson AO (2018) A three-ring circus: Metabolism of the three ... Cohen NR, Lobritz MA, Collins JJ (2013) Microbial persistence and the road to drug resistance. Cell Host Microbe Rev 13:632-642 ... Uotila JS, Kitunen VH, Coote T, Saastamoinen T, Salkinoja-Salonen M, Apajalahti JHA (1995) Metabolism of halohydroquinones in ...
Bioremediation and Biotransformation History History of Xenobiotic Metabolism at the Wayback Machine (archived July 13, 2007) ... of Minnesota Biocatalysis/Biodegradation Database SPORCalc Drug metabolism Small Molecule Drug Metabolism Drug metabolism ... For example, the rate of metabolism determines the duration and intensity of a drugs pharmacologic action. Drug metabolism ... The study of drug metabolism is called pharmacokinetics. The metabolism of pharmaceutical drugs is an important aspect of ...
Biotransformation of xenobiotics in the human colon and rectum and its association with colorectal cancer, Drug Metabolism ... Drug Metabolism Reviews, 2016, 48, 1, 47. CrossRef. *4. Se-Jung Park, Bitna Yi, Ho-Sun Lee, Woo-Yeon Oh, Hyun-Kyung Na, ... Hanne R. Hagland, Kjetil Søreide, Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and ... Because UGT2B17 metabolizes certain nonsteroidal anti-inflammatory drugs and flavonoids with antioxidative properties, ...
This N-methylation enzymatic activity plays an important role in the biotransformation of drugs and xenobiotics, and also ... This regulates AMPKα1 activity towards ACC1, an important regulator of fatty acid metabolism (15). Mutation of NDKB/NM23-H2 at ... This regulates AMPKα1 activity towards ACC1, an important regulator of fatty acid metabolism (15). Mutation of NDKB/NM23-H2 at ... Background: Nod1/CARD4 is a cytosolic protein structually related to Apaf-1 and plant drug-resistance proteins that has been ...
... constitute a class of enzymes that play important roles in the hydrolytic metabolism of drugs and other xenobiotics. Patients ... provide a molecular explanation linking cytokine secretion directly to the decreased capacity of hydrolytic biotransformation. ... Such a reversal was observed with other ester drugs, including anticancer agent irinotecan and anti-influenza agent oseltamivir ... The altered cellular responsiveness was observed when drugs were assayed at sub- and low-micromolar concentrations, suggesting ...
Cytochrome P450 is one of the enzymes involved in biotransformation of xenobiotics and various hydrophobic endogenous compounds ... Metabolism of drugs by microsomal cytochrome P450 plays an important role in the pharmacological and toxicological effects of ... drugs and in the drug-drug and food-drug interactions in humans (77, 78). Diet modulates cytochrome P450 to determine the ... These findings indicate that the consumption of the pro-milk extract may enhance the clearance of xenobiotics and drugs at ...
UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by ... Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to ... Drug metabolism; E(Het); E(Hom); E(Wt); G; Guanine; HIV; Het; Heterozygous; Hom; Homozygous; MD; NSAID(s); PK; PharmGKB; ... Evidence for effects of potential clinical relevance exists for 19 drugs, but the data are not sufficient to assess effect size ...
... regulated by structurally diverse xenobiotics that in turn affect xenobiotic drug metabolism or other P450-dependent drug-drug ... in the liver and intestines and is involved in the biotransformation of a variety of structurally diverse xenobiotics (7). ... As expected, cisplatin (a drug that does not affect CYP450 gene expression or CYP450 metabolism) and PCN (a drug that only ... suggesting that both drugs induce drug metabolism enzyme activity in vivo.. In summary, the novelty of our findings is that we ...
... with disturbed bile acid conjugation and drug metabolism. Cholestasis was preceded by disruption of the bile acid and organic ... In a long-term rat model of faecal peritonitis, biotransformation and hepatobiliary transport were impaired, depending on ... At 15 h there was hepatocellular accumulation of bilirubin, bile acids, and xenobiotics, ... All aspects of hepatic biotransformation are affected, with severity relating to subsequent prognosis. Detected changes ...
However, knowledge about the effects of these polymorphisms is rarely used for the individualization of drug therapy. Here, we ... catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. ... UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by ... Here, we present a quantitative systematic review of clinical studies on the impact of UGT variants on drug metabolism to ...
  • If this modification ends in mineral compounds like CO2, NH4+, or H2O, the biotransformation is called mineralisation. (
  • Biotransformation of xenobiotics can dominate toxicokinetics and the metabolites may reach higher concentrations in organisms than their parent compounds. (
  • These bioremediation and biotransformation methods harness the naturally occurring, microbial catabolic diversity to degrade, transform or accumulate a huge range of compounds including hydrocarbons (e.g. oil), polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), pharmaceutical substances, radionuclides and metals. (
  • Functional genomic and metagenomic approaches are increasing our understanding of the relative importance of different pathways and regulatory networks to carbon flux in particular environments and for particular compounds and they are accelerating the development of bioremediation technologies and biotransformation processes. (
  • Foreign Compounds and Intermediary Metabolism: Sulfoxidation Bridges the Divide. (
  • Xenobiotic-metabolizing enzymes (XME) are responsible for the biotransformation of a vast range of compounds. (
  • It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. (
  • More generally, xenobiotic metabolism (from the Greek xenos "stranger" and biotic "related to living beings") is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. (
  • These reactions often act to detoxify poisonous compounds (although in some cases the intermediates in xenobiotic metabolism can themselves cause toxic effects). (
  • Drug metabolism often converts lipophilic compounds into hydrophilic products that are more readily excreted. (
  • The major challenge faced by xenobiotic detoxification systems is that they must be able to remove the almost-limitless number of xenobiotic compounds from the complex mixture of chemicals involved in normal metabolism. (
  • In contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid-soluble xenobiotics using membrane barriers. (
  • Small molecule organic drugs are considered xenobiotics-compounds foreign to our native metabolome. (
  • The metabolic reconstruction for Bt AOA showed that the organism has been naturally exposed to various chlorophenolic compounds including PCP and other xenobiotics. (
  • This study provides a comprehensive understanding of the role of Bt AOA in PCP degradation and its potential exploitation for bioremediation of other xenobiotic compounds. (
  • These studies show that some azole compounds repress the coordinated activation of genes involved in drug metabolism by blocking PXR activation. (
  • Xenobiotic compounds are classified as any foreign chemical substance inside the biological system. (
  • Compounds foreign to an organism's normal biochemistry are metabolized by enzymatically catalysed biotransformations. (
  • A candidate drug faces a system that has evolved to prevent exposure of foreign compounds in the body by metabolising enzymes. (
  • Biotransformation of drugs and endogenous compounds catalyzed by specific enzymes. (
  • The process of biotransformation, i.e., the enzymatic alteration of foreign or xenobiotic compounds, is conventionally divided into two phases. (
  • Two groups of enzymes are known to handle metabolism of harmful compounds. (
  • Isoforms in the CYP groups 1, 2, and 3 mediate metabolism of many exogenous compounds. (
  • It contains over 3144 microarrays of gene expression data corresponding to rat livers treated with 131 compounds (most are drugs) at two doses (control and high dose) in a repeated schedule containing four separate time points (4-, 8-, 15- and 29-day). (
  • 2 This biotransformation process uses cosubstrate 3'-phosphoadenosine-5'-phosphosulphate to transform the substrates to water-soluble compounds through catalysis by sulphotransferase enzymes, 3,4 giving rise to the sulphonated product and the 3'-phosphoadenosine 5'-phosphate. (
  • Biotransformation of drugs and other xenobiotic compounds involves a myriad of drug-metabolizing enzymes, of which the cytochrome P450 (P450) monooxygenases are important members ( Porter and Coon, 1991 ). (
  • Phase II drug metabolizing enzymes play an important role in biotransformation of endogenous compounds and xenobiotics to more easily excretable forms as well as in the metabolic inactivation of pharmacologically active compounds. (
  • Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more water-soluble compounds. (
  • Cytochrome P450 (CYP) enzymes metabolize endogenous compounds such as steroid hormones, fatty acids, and xenobiotics, including drugs and carcinogens. (
  • Nevertheless, basal expression and up-regulation of extrahepatic CYP enzymes can significantly affect local disposition of xenobiotics or endogenous compounds in peripheral tissues and thus modify their pharmacological/toxicological effects or affect absorption of xenobiotics in the systemic circulation [9]. (
  • The principal classes of xenobiotics of medical relevance are drugs, chemical carcinogens, and various compounds that have found their way into our environment by one route or another, such as polychlorinated biphenyls (PCBs) and certain insecticides. (
  • Humans are exposed daily to a wide variety of foreign compounds called xenobiotics -substances absorbed across the lungs or skin or, more commonly, ingested either unintentionally as compounds present in food and drink or deliberately as drugs for therapeutic or "recreational" purposes. (
  • The discussion that follows is applicable to xenobiotics in general (including drugs) and to some extent to endogenous compounds. (
  • The body generally identifies drugs as foreign substances andenzymes such as the Cytochrome P450 superfamily are heavily involved in the metabolism of foreign (xenobiotic) substances.The human body is armed with numerous metabolic enzymes that mediate the conversion of xenobiotic compounds to more excretable compounds. (
  • Phase I and Phase II reactions complement each other in the modification and excretion of xenobiotic compounds. (
  • PXR and CAR ligands are largely exogenous compounds, indicating complex interaction between xenobiotics and the body. (
  • A number of factors which are known to alter the biliary excretion of xenobiotics, as well as the current concepts of the physiological mechanisms responsible for the excretion of foreign compounds, have been enumerated. (
  • In most cases, the drug action terminates by enzyme-catalyzed conversion to inactive (or less active) compounds and/or elimination via the kidneys or other routes. (
  • Therefore, biotransformation of compounds into more polar (hydrophilic) structures is essential for complete removal of the drug. (
  • Many drugs undergo several sequential biotransformation reactions that are catalyzed by specific enzyme systems, primarily in the liver, which may also catalyze the biotransformation of endogenous compounds (ie, steroids). (
  • They can exert the identical selective oxyfunctionalization of organic compounds and drugs as known for CYP enzymes with hydrogen peroxide being used as sole cosubstrate. (
  • Drug transporters belonging to two major super-families of membrane-associated proteins, the solute carriers (SLCs), which primarily function as a cellular drug influx mechanism, and the ATP-binding cassette (ABC) transporters which in contrast, efflux drugs/ compounds from cellular targets, are known to play a vital role in overall drug disposition (i.e., drug distribution to target tissues/cells and drug clearance from the liver and kidney). (
  • The construction of genetically engineered mammalian cells for the production of a specific P450 isozyme and the application of these cell lines in drug metabolism, mutagenicity and toxicity studies are described in detail. (
  • The liver's unique metabolism and relationship to the gastrointestinal tract make it an important target of the toxicity of drugs and xenobiotics. (
  • Hepatic toxicity as a result of drugs and environmental toxins presents a wide spectrum of clinical disease. (
  • Children who take medications that are known to be hepatotoxic, such as anticonvulsants and antineoplastic drugs, need frequent monitoring for evidence of hepatic toxicity. (
  • Studies of the biochemical and enzymatic properties of these enzymes and their molecular genetics and regulation of gene expression and activity have greatly enhanced our understanding of several aspects of clinical pharmacology such as pharmacokinetic variability, drug toxicity, and drug interactions. (
  • A recent randomized prospective clinical study has shown that CYP3A activity-guided docetaxel dosing results in more uniform drug pharmacokinetics and less toxicity than traditional body surface area-based dosing ( 5 ). (
  • The activity and the potential toxicity of numerous drugs are strongly influenced by their biotransformation, mainly accomplished by the cytochrome P450 enzymes, one of the most versatile enzyme systems. (
  • Paine A (1990).The maintenance of cytochrome P$%) in rat hepatocyte cultures: Some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the P450 system.Chem-biol Interact. (
  • Skett P. (1994) Problems in using isolated and cultured hepatocytes for xenobiotic metabolism-based toxicity testing - solutions? (
  • This new edition goes beyond LC-MS and features all-new chapters on how to evaluate drug absorption, distribution, metabolism, and excretion, potential for hepatic and renal toxicity, immunogenicity of biotherapeutics and translational tools for predicting human dosage, safety and efficacy of small molecules and biologics. (
  • Our findings, with clinically relevant therapeutic drugs (nicotine, coumarin, chlorzoxazone, and acetaminophen) and the prodrug (tamoxifen) as P450 substrates, reveal that P450 ERAD disruption could influence therapeutic drug response and/or toxicity, warranting serious consideration as a potential source of clinically relevant drug-drug interactions (DDIs). (
  • Interaction of herbal products with conventional drugs is also a potential source of toxicity. (
  • In the liver, circadian rhythms produce oscillation in drug Phase-I, Phase-II, and Phase-III (transporters) metabolism genes, which in turn would affect drug disposition and detoxication, resulting in diurnal variations of efficacy and toxicity when drugs are given at different times of the day. (
  • Electron transfer plays a vital role in drug metabolism and underlying toxicity mechanisms. (
  • Currently, pharmaceutical research relies on pharmacokinetics (PK) and absorption, distribution, metabolism, elimination and toxicity (ADMET) measurements to understand and predict drug reactions in the body. (
  • Metabolic stability (and toxicity) prediction in the early phases of the drug discovery and development process is key in identifying a suitable lead compound for optimisation. (
  • Voltammetric methods have the potential to overcome the significant barrier of new drug failure rates, by giving insight into phase I metabolism events which can have a direct bearing on the stability and toxicity of the parent drug being dosed. (
  • Herein, we report for the first time a data-mining investigation into the voltammetric behaviour of reported drug molecules and their correlation with metabolic stability (indirectly measured via t ½ ), as a potential predictor of drug stability/toxicity in vivo. (
  • Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. (
  • Horning MG, Mitchell J. Drug metabolism and drug toxicity . (
  • Metabolism and toxicity of various xenobiotics in vitamin B1 deficiency and after administration of thiamine and thiamine diphosphate. (
  • Much of the impetus for this area of research has come from the field of pharmacogenetics, which is primarily concerned with the study of genetic variation in drug efficacy and toxicity. (
  • It has been recognized for many decades that individual differences in response to pharmacological treatment, exhibited as drug toxicity or a lack of therapeutic effect, are often due to genetic differences that result in altered rates of biotransformation (metabolism). (
  • As a foundation for learning, we will provide examples of drugs and other xenobiotics that exhibit toxicity related to biotransformation. (
  • The slower elimination of CPA in CL-LCN mice compared with LCN mice suggests a role for extrahepatic P450 in the in vivo metabolism of CPA and demonstrates the utility of the CL-LCN model in determining the role of extrahepatic P450 enzymes in drug metabolism and chemical toxicity. (
  • For example, extrahepatic tissue contributions to systemic metabolism or local drug toxicity could be inferred from any differences in metabolism or toxicity between the LCN and CL mouse models. (
  • 21. The Role of Drug Metabolism in Toxicity (Carl D. Davis and Umesh M. Hanumegowda). (
  • The acronym is sometimes extended to include drug transport (AMDET) or drug toxicity (ADME-Tox). (
  • Moreover, since the potential participation of muscles is a fact in pharmacokinetics of many therapeutic drugs, expression of CYPs in skeletal muscle may play an important role in drug-dependent toxicity. (
  • The use of human drug metabolites as authentic standards to evaluate their toxicity is essential for drug development. (
  • Individual differences in pharmacokinetics may cause extensive variability in drug efficacy, toxicity and adverse drug reactions, and represent a major concern in drug development. (
  • Drug metabolizing enzymes and transporters plays vital role in the disposition, pharmacokinetics as well as efficacy and toxicity of many antituberculosis (anti-TB) and antiretroviral (ARVs) drugs. (
  • These transporters are also thought to be contributor in pharmacokinetic drug-drug interactions, clinical response as well as toxicity [2][3]. (
  • Since the drug pharmacokinetics can be significantly altered by both transporters and enzyme mediated DDIs, it can potentially affect to the therapeutic efficacy or toxicity of a drug [6]. (
  • In the field of Environmental Microbiology, genome-based global studies open a new era providing unprecedented in silico views of metabolic and regulatory networks, as well as clues to the evolution of biochemical pathways relevant to biotransformation and to the molecular adaptation strategies to changing environmental conditions. (
  • Age-related sensitivity to drugs is attributable in part to differences in metabolic activity. (
  • The developmental changes that occur in the liver determine the rate and metabolic pathways used in the disposition of drugs and other xenobiotics. (
  • Such information is essential in the development of methods to predict metabolism of drugs and to understand metabolic effects of genetic polymorphism in biotransformation enzymes. (
  • It is widely appreciated that as a xenobiotic travels through an organism and interacts with the biochemical machinery of a living system, it most probably will undergo a number of metabolic alterations usually leading to a cluster of differing chemical species. (
  • 1991 ). Therefore, knowledge of the extent of biliary excretion of drug candidates in the early stages of drug development may be as important as absorption and metabolic properties when selecting drug candidates. (
  • The mathematical models used in predicting the pharmacokinetic clearance of a drug from in vitro estimates of intrinsic clearance and the principles of quantitative in vitro-in vivo scaling of metabolic drug interactions are also discussed. (
  • Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. (
  • Understanding and manipulating these enzyme/proteinbased metabolic mechanisms is an area of increasing focus for improved drug targeting to specific organs, tissues, and cell types, as well as enabling creative strategies for improving bioavailability and circulating time. (
  • An added complexity for drug designers is the effect of human polymorphisms of metabolic enzymes on drug metabolism. (
  • In drug discovery, it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. (
  • UDP-glycosyltransferases (UGTs) participate in the metabolic inactivation of anthelmintics and other xenobiotic substrates through their conjugation with activated sugar, which drives the elimination of the xenobiotics due to enhanced solubility. (
  • Glycosidation or conjugation of activated sugar to a lipophilic compound, in general, is performed by UDP-glycosyltransferases (UGTs), during the second phase of biotransformation, causing the metabolic inactivation of xenobiotic substrates. (
  • The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed through a series of steps into another chemical, each step being facilitated by a specific enzyme. (
  • A striking feature of metabolism is the similarity of the basic metabolic pathways among vastly different species. (
  • Amino acids also contribute to cellular energy metabolism by providing a carbon source for entry into the citric acid cycle (tricarboxylic acid cycle), especially when a primary source of energy, such as glucose, is scarce, or when cells undergo metabolic stress. (
  • Predicting metabolic sites is important in the drug discovery process to aid in rapid compound optimisation. (
  • Metabolic stability is a critical aspect in the drug discovery process. (
  • Another method uses historic metabolic biotransformation data from the literature exclusively [ 3 ]. (
  • This metabolic redox biotransformation of the drug facilitates the elimination of the xenobiotic as a more polar drug metabolite [ 2 ]. (
  • However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. (
  • In general, the sources seem to use the term 'biotransformation' to describe the metabolic processes which chemically alter the drugs after they have been administered to an organism. (
  • The method builds on a database of atom environments found in molecules known to undergo metabolic transformation, such as the data found in the Symyx(R) (previously MDL) Metabolite database , which contains over 80.000 metabolic transformations of xenobiotics, curated from reports in scientific literature. (
  • Thus, it is difficult to accurately predict, from the results of in vitro studies, the contributions of P450 enzymes to the metabolic activation and disposition of a given drug in vivo. (
  • 10. Structural Modifications of Drug Candidates: How Useful Are They in Improving Metabolic Stability of New Drugs? (
  • The role of skeletal muscle as a site of extrahepatic xenobiotic metabolism has not been sufficiently addressed, despite accounting for around 45% of total body weight and it is characterized by high metabolic rate and blood flow. (
  • While P450s are responsible for the metabolic clearance of drugs from the human body, this is not always a benevolent process: sometimes metabolites are generated that are chemically reactive and may cause mutagenic or other toxic effects. (
  • Cytochrome oxidase is not mentioned as an enzyme in the metabolism of xenobiotics but Cytochrome P450 and Hydroxylation reactions are involved in Phase-1 metabolic reactions and Methylation forms a part of phase II reactions. (
  • Following entry to the body, drug molecules undergo metabolic transformations to derivatives known as metabolites . (
  • These metabolic transformations are sometimes referred to as biotransformations . (
  • Human CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 participate in about 90% of known phase I drug metabolic reactions. (
  • 1994 ). Although, the biotransformation of xenobiotics takes place mostly in the liver, some extrahepatic cytochrome P450 complexes (e.g., gastrointestinal, renal and pulmonary) contribute substantially to the total metabolic potential of the living mammals. (
  • 2006 ). Metabolic processes performed by the gut mucosa may affect uptake, efflux and transport of orally delivered pharmaceuticals and dietary xenobiotics by cells, tissues and organs (Benet et al. (
  • Inhibition-based metabolic drug-drug interactions: predictions from in vitro data cheap levitra oral jelly 20mg with visa . (
  • Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors, and clinical con- firmation of a predicted interaction with ketoconazole. (
  • The current understanding of drug-drug interactions involving the first-line antituberculosis and antiretroviral (ARVs) drugs are reviewed and summarized in this article emphasizing the role of drug transporters and metabolic enzymes. (
  • It is found that several clinical drug-interactions are caused by the phase I and II metabolic enzymes (cytochrome-P-450s, CYPs, UDP-glucuronosyltransferases, UGTs) and uptake/ efflux transporters, particularly permeability glycoprotein, brest cancer resistance protein, multidrug resistance protein and solute carrier transporters). (
  • The alterations of response may result from the change in drug disposition which is believed to cause by induction or inhibition of transporters or metabolic enzymes and drug transporters play role in drug absorption, distribution, metabolism and excretion (ADME), those DDIs are known for pharmacokinetic interactions [1]. (
  • Generally, DDIs based on metabolism are due to induction and/or inhibition of metabolic enzymes (CYP450s or UGTs), are considered as most prominent cause [7]. (
  • Human liver microsomes catalyzed the NADPH-dependent metabolism of tramadol to the two primary tramadol metabolites, namely, O -desmethyl-tramadol (metabolite M1) and N -desmethyl-tramadol (metabolite M2). (
  • In addition, tramadol was also metabolized to two minor secondary metabolites (each comprising ≤3.0% of total tramadol metabolism), namely, N , N -didesmethyl-tramadol (metabolite M3) and N , O -didesmethyl-tramadol (metabolite M5). (
  • Hepatic drug metabolism, often with an imbalance between the generation of toxic metabolites and detoxification processes, can influence the degree of hepatotoxicity. (
  • The drug metabolites of 1 in nonclinical. (
  • Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters, Second Edition, is completely updated to provide an overview of the last decade's numerous advances in analytical technologies for detection and quantification of drugs, metabolites, and biomarkers. (
  • A new software application called Metabolizer has been developed to enumerate all metabolites and to predict the major ones of the given drugs or other xenobiotics. (
  • While both occur, the major metabolites of most drugs are detoxication products. (
  • These xenobiotics often undergo biotransformation, a complex process that plays a critical role in xenobiotic elimination or bioactivation to toxic metabolites. (
  • Our results indicate that this tool is useful for predictive xenobiotic metabolomics, providing new and important insights into metabolites and the interrelationship between diverse chemicals that hitherto may have remained unnoticed. (
  • The Research Starter Grant enabled the Bumpus Laboratory to begin to pursue the long-term goal of gaining an understanding the unique pharmacology/toxicology of cytochrome P450 (P450)-dependent metabolites of antiretroviral drugs and the role of drug metabolites in modulating tissue-specific pharmacokinetic-pharmacodynamic relationships of these drugs. (
  • Through our work with dapvirine the lab established that the several of the major drug metabolizing P450s are present and active in human colorectal and vaginal tissues and that the metabolites formed in these tissues differ from those formed by liver. (
  • Often these break-down products (metabolites) are more hydrophilic than their parent drug.Metabolites may possess a different level of activity as the starting compound or none at all. (
  • We offer a large range of Biochemicals for Metabolism Studies (Probe Substrates, Metabolites and Inhibitors, most of which are listed in the draft FDA guidance #6695 dft) as well as microsomes containing recombinant human CYP450s. (
  • Being the major elimination route for many drugs, CYP450 enzymes play a very important role in the xenobiotics detoxication, but may also lead to toxic or tumorigenic metabolites. (
  • Those metabolites are either produced by chemical synthesis or by biotransformation - biocatalysis reactions. (
  • Bertin Bioreagent also proposes a fully integrated analytical and preparative platform using chemical synthesis, biotransformation or chemoenzymatic technologies for the production of conjugated metabolites. (
  • Quantification of coincident biotransformation of xenobiotics and endogenous metabolites in tumor tissues is critical for understanding exposure-response relationships, but currently demands an impractical degree of analytical sensitivity and spatial resolution. (
  • Liquid chromatography-tandem mass spectrometry (LC-MS/MS) characterization of endogenous and xenobiotic metabolites is a cornerstone of drug development, but most methods involve sample extractions that sacrifice spatial resolution for analytical sensitivity. (
  • Most drugs undergo biotransformation to produce more polar metabolites than the administered drug. (
  • The high yield of 4-OH-CPA UPO and its biological activity demonstrate that UPOs can be efficiently used to produce CYP-specific drug metabolites for pharmacological assessment. (
  • Even though xenobiotic metabolism during biotransformation serves mostly as biochemical detoxification process, resulting metabolites might also cause adverse drug reactions and complications (Kirchmair et al. (
  • Based on the therapeutic and toxic effects of both the parent drug and its metabolites, the clinical consequences depends on the CYP450 enzyme induction or inhibition and this may be particularly significant to those drugs has narrow therapeutic window because DDIs based on metabolism may cause changes in the concentration of drug up to 10 fold whose biotransformation is induced or inhibited [8]. (
  • Many drugs undergo biliary excretion, although the extent of secretion in bile often is difficult to quantitate, particularly in humans. (
  • Alterations in biliary excretion due to disease states or drug interactions may have important pharmacologic and/or toxicologic implications. (
  • The elucidation of biliary excretion properties of drug candidates is also a critical issue in the drug discovery and development process. (
  • In addition, current approaches cannot be used to efficiently examine biliary excretion processes for a large number of drug candidates. (
  • The metabolism of xenobiotics is often divided into three phases:- modification, conjugation, and excretion. (
  • One aspect of human metabolism is the excretion of xenobiotics-e.g., drugs or carcinogens-by biochemical transformations. (
  • Metabolism and excretion of exogenously administered therapeutic and diagnostic agents as well as environmental exposures are other major functions. (
  • Renal excretion plays a pivotal role in terminating the biologic activity of some drugs, particularly those that have small molecular volumes or possess polar characteristics, such as functional groups that are fully ionized at physiologic pH. (
  • Orally-administered drugs commonly undergo the processes of absorption, distribution, metabolism and excretion in vivo. (
  • the pathways of drug metabolism can be divided into: phase І phase II Drugs can undergo one of four potential biotransformations: Active Drug to Inactive Metabolite, Active Drug to Active Metabolite, Inactive Drug to Active Metabolite, Active Drug to Toxic Metabolite (biotoxification). (
  • Major methodological breakthroughs in recent years have enabled detailed genomic, metagenomic, proteomic, bioinformatic and other high-throughput analyses of environmentally relevant microorganisms providing unprecedented insights into biotransformation and biodegradative pathways and the ability of organisms to adapt to changing environmental conditions. (
  • Other products of metabolism-substances that enter the body through other pathways and substances that are not extracted from the portal blood during the first pass-reach the liver by the hepatic artery. (
  • Among its related pathways are Metabolism and Cytochrome P450 - arranged by substrate type . (
  • These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. (
  • These pathways are also important in environmental science, with the xenobiotic metabolism of microorganisms determining whether a pollutant will be broken down during bioremediation, or persist in the environment. (
  • GO and KEGG database are used to identify metabolism pathways and related genes. (
  • Pathways of propranolol metabolism. (
  • Among its related pathways are Metabolism and Aflatoxin activation and detoxification . (
  • This course provides a strong conceptual foundation of enzymology and mechanisms of drug biotransformation pathways. (
  • The biological meaning underlying each topic was interpreted using diverse sources of information such as functional analysis of the pathways and therapeutic uses of the drugs. (
  • General pathways of xenobiotic biotransformation and their major subcellular location. (
  • This drug class is a cornerstone of HIV therapy and we were the first to report the pathways of both phase 1 and phase 2 metabolism of 2 (rilpivirine and etravirine) of the 4 currently FDA approved and marketed drugs in this class while also demonstrating that these drugs autoinduce their own metabolism via activation of the pregnane X receptor. (
  • However, there is not much information available about age-dependent changes of intestinal biotransformation pathways. (
  • Hint of in vivo drug-drug interactions from in vitro data: striking of incorporating correspondent pathways of stimulant elimination and inhibitor absorption rate unwavering purchase cialis extra dosage 40mg mastercard . (
  • In studies with characterized human liver microsomal preparations, good correlations were observed between tramadol metabolism to M1 and M2 and enzymatic markers of CYP2D6 and CYP2B6, respectively. (
  • Also there is other approach of biotransformation called enzymatic biotransformation. (
  • This enzymatic modification (biotransformation) occurs by two types of reactions, phase I and phase II, which differ regarding the type of modification introduced. (
  • Since the major class of reactions in phase I metabolism are oxidation reactions [ 3 ], also non-enzymatic methods could be used for rapid phase I reactions to eliminate drug candidates with an undesired metabolism. (
  • Under physiological conditions, humans exhibit mechanisms responsible for enzymatic metabolism or biotransformation of xenobiotics. (
  • Drug metabolism is the metabolism of drugs , their biochemical modification or degradation, usually through specialized enzymatic systems. (
  • A series of chemical changes in a compound (e.g., a drug), which occur within the body (e.g., by enzymatic activity). (
  • Phase II metabolism is mediated by several different enzymatic systems, the most important being the UDP glucuronosyltransferases. (
  • Drug Metabolism and Pharmacokinetics (DMPK) is an official online journal of the Japanese Society for the Study of Xenobiotics (JSSX), and it replaces the JSSX's former journal, Xenobiotic Metabolism and Disposition. (
  • The study of drug metabolism is called pharmacokinetics. (
  • However, there is evidence of the existence of large monogenetic functional polymorphisms affecting pharmacokinetics and suggesting a potential use of UGT polymorphisms for the individualization of drug therapy. (
  • Therefore, approaches to control or "unify" metabolism that include both biotransformation and transporter function could result in uniform pharmacokinetics and pharmacodynamics, as well as increased efficacy and predictability of drug treatment. (
  • The journal offers new hypotheses of interest to diverse groups of medical professionals, including pharmacologists, toxicologists, chemists, microbiologists, pharmacokinetics, immunologists and mass spectroscopists, as well as enzymologists working in xenobiotic biotransformation. (
  • In these types of reactions, a polar group is either introduced or unmasked, so the drug molecule becomes more water-soluble and can be excreted. (
  • These reactions act in concert to detoxify xenobiotics and remove them from cells. (
  • As the major class of reactions in phase I metabolism is oxidation reactions, oxidation of drugs with TiO 2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. (
  • The biotransformation, phase I, plays an important role in the deactivation of drugs and activation of prodrugs and comprises reactions such as oxidation, reduction, and hydrolysis. (
  • This involves the biotransformation based on phase I and phase II reactions. (
  • The impact of bio catalysis in the future will be the enlarge of ability to use enzymes to catalyze chemical reactions in industrial processes, including the manufacture of drug material, flavors, fragrances, electronic chemicals, polymers-chemicals that literally impact almost every facet of your life. (
  • Metabolism (/məˈtæbəlɪzəm/, from Greek: μεταβολή metabolē, "change") is the set of life-sustaining chemical reactions in organisms. (
  • The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transport of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism or intermediate metabolism. (
  • Enzymes are crucial to metabolism because they allow organisms to drive desirable reactions that require energy that will not occur by themselves, by coupling them to spontaneous reactions that release energy. (
  • Many proteins are enzymes that catalyze the chemical reactions in metabolism. (
  • This provides the opportunity for drug-drug and drug-chemical interactions or reactions. (
  • Phase I and Phase II reactions are biotransformations of chemicals that occur during drug metabolism. (
  • In the case of pharmaceutical drugs, Phase I reactions can lead either to activation or inactivation of the drug. (
  • The mechanisms are quite well understood, but there is still a tremendous variation in reactions that lead to biotransformations. (
  • Examples of biotransformation of drugs for each group of reactions. (
  • Phase I and II reactions are catalyzed by enzymes collectively known as xenobiotic metabolism enzymes (XMEs). (
  • 22. Allergic reactions to Drugs (Mark P. Grillo). (
  • Phase II biotransformation reactions (also conjugation reactions ) generally serve as a detoxifying step in drug metabolism. (
  • The purpose of phase II biotransformation is to perform conjugating reactions. (
  • Phase II biotransformation reactions include glucuronidation, sulfonation (more commonly called sulfation), acetylation, methylation, and conjugation with glutathione (mercapturic acid synthesis), which usually result in increased hydrophilicity and elimination. (
  • For example, acetylation and methylation are biotransformation reactions that can actually decrease the water solubility of certain xenobiotics. (
  • Q. 1 In metabolism of xenobiotics all of the following reactions occur in phase one except? (
  • Drug metabolism can be divided into the Phase I reactions (functionalisation) and the Phase II reactions (conjugation). (
  • Phase I biotransformations include oxidation , reduction , and hydrolysis reactions. (
  • Often these reactions involve the introduction of polar functional groups such as -OH to drug molecules to make them more hydrophilic. (
  • For instance, a drug containing a benzene group may undergo Phase I reactions (e.g.hydroxylation of the ring, favouring the para position). (
  • Reductive drug metabolism reactions, which tend to be facilitated by reductases, can occur with drugs containing carbonyl, azo, and nitro groups.Carbonyl groups can be reduced to alcohols whereas nitro and azo groups are reduced to amino derivatives. (
  • The pharmacokinetic DDIs are responsible for approximately 20-30% of the adverse drug reactions in general population, they also account for about 10% of the cases under emergency department and contribute 3-5% of the medication errors in-patients [4][5]. (
  • This chapter reviewed the relevant literature and a dozen of publications from our work, discussed the interactions of circadian clock genes with drugs and/or toxicants to better understand the importance of circadian clock gene expression as novel targets in Pharmacology and Toxicology. (
  • Other activities will include online discussions of current news articles and scientific publications that relate to drug metabolism, toxicology and biochemistry. (
  • Molecular Toxicology reflects the revolution that toxicology has undergone in the last decade, as the molecular and genetic basis of the science--including drug metabolism, carcinogenesis, programmed cell death, and DNA repair--has been elucidated. (
  • Her research program is focused on defining the contribution of drug metabolism to the pharmacology and toxicology of drugs used to treat and prevent HIV infection. (
  • The metabolism of cis -tramadol has been studied in human liver microsomes and in cDNA-expressed human cytochrome P-450 (CYP) isoforms. (
  • Tramadol metabolism in human liver microsomes to M1 and M2 was markedly inhibited by the CYP2D6 inhibitor quinidine and the CYP3A4 inhibitor troleandomycin, respectively. (
  • By kinetic analysis and the results of the reaction phenotyping studies, tramadol metabolism in human liver is catalyzed by multiple CYP isoforms. (
  • The decreased capacity of the neonatal liver to metabolize, detoxify, and excrete xenobiotics explains the prolonged action of drugs such as phenobarbital, theophyline, and phenytoin. (
  • Drug or environmental xenobiotic-induced hepatotoxicity should be considered in the setting of identified exposure or when other causes of childhood liver disease are excluded. (
  • For understanding the variable effects of environmental xenobiotic exposures in children, a basic review of liver anatomy, physiology, and development is necessary. (
  • The liver performs many essential functions, including the production of bile, regulation of plasma proteins and glucose, and biotransformation of drugs and toxins. (
  • The liver is the first organ that comes into contact with enterally absorbed nutrients and xenobiotics via the portal vein. (
  • 1 The newborn liver manifests many unique physiologic traits that are likely part of the normal developmental process and may predispose the liver in infants and children to the toxic effect of xenobiotics at levels that may be safe for the adult. (
  • Cytochrome P 450 3A4 is expressed predominantly in the liver and intestines and is involved in the biotransformation of a variety of structurally diverse xenobiotics ( 7 ). (
  • Focuses on the role of drug metabolism enzymes, transporters in disposition and drug-drug interactions, as well as strategies for evaluating drug metabolism and safety using advanced liver and kidney models. (
  • Quantitatively, the smooth endoplasmic reticulum of the liver cell is the principal organ of drug metabolism, although every biological tissue has some ability to metabolize drugs. (
  • Factors responsible for the liver 's contribution to drug metabolism include that it is a large organ, that it is the first organ perfused by chemicals absorbed in the gut , and that there are very high concentrations of most drug-metabolizing enzyme systems relative to other organs. (
  • detoxification, endurance training, IL-6, nuclear receptors, drug metabolism The liver is the main organ for the biotransformation of xenobiotics, presenting high expression and activity of the cytochrome P450 (CYP) system. (
  • Modulation of aflatoxin B1 carcinogenicity, genotoxicity and metabolism in rat liver by dietary carotenoids: evidence for a protective effect of CYP1A inducers. (
  • Activity of enzymes of xenobiotic metabolism in the liver of rats with vitamin A deficiency and mycotoxicosis T-2. (
  • Liver, the largest glandular organ in the body, plays a dynamic role in metabolism, biotransformation of proteins, carbohydrates, lipids and also detoxification of different endogenous and exogenous xenobiotics and drugs. (
  • After i.p. injection of CPA at 100 mg/kg, the t 1/2 and the area under the concentration-time curve for plasma CPA were significantly increased in mice deficient in liver CPR compared with wild-type controls, indicating a lower rate of metabolism, with the effects greater in CL-LCN mice than in LCN mice. (
  • Expression of CXR is restricted to tissues where drug induction of CYPs predominantly occurs, namely liver, kidney, small intestine, and colon. (
  • Since the expression of the majority of the isoforms appears to be very low in extrahepatic tissues in comparison with the predominant expression in adult liver, the role of these enzymes in overall biotransformation and total body clearance is minor. (
  • The metabolism occcurs more or less in every tissue but mainly in the liver. (
  • Both liver microsome and cytosol could catalyze the biotransformation of TETA. (
  • Among these CYPs, CYP3A4 is the most abundant isoform in human liver and intestine, and plays significant roles in the biotransformation of the greatest number of endobiotics and xenobiotics. (
  • This drug interaction was caused by inhibition of CYP1A and CYP3A enzyme activities in rainbow trout liver. (
  • It has been established beyond doubt that, as well as the liver, the small intestine is an important site of first-pass metabolism of numerous drugs, food components and toxic xenobiotics. (
  • The elimination of many drugs begins with a first pass effect , where orally administered drugs absorbed from the gastrointestinal tract into circulation pass through the liver before reaching targeted sites of action. (
  • The biotransformation of drugs is variable between individuals and is dependent on a multitude of factors, including age, diet, genetics, liver function, prior administration of the drug, and drug interactions. (
  • This issue of Biofiles is devoted to our diverse portfolio of reagents, enzymes, and labware designed for the analysis of drug delivery, absorption, and metabolism. (
  • There are both direct and indirect mechanisms through which the gut microbiome can influence xenobiotic metabolism to modulate efficacy, absorption, and bioavailability. (
  • Biotransformation occur between absorption and elimination from kidneys. (
  • In the gastrointestinal GI tract(GIT), metabolism prior to absorption via gut microflora or enzymes in the GI mucosa may occur. (
  • Drug metabolism also affects multidrug resistance in infectious diseases and in chemotherapy for cancer, and the actions of some drugs as substrates or inhibitors of enzymes involved in xenobiotic metabolism are a common reason for hazardous drug interactions. (
  • This report describes studies undertaken to explore the characteristics of hPXR stimulation and mechanisms of drug-receptor interactions in vitro with new anti-tubulin drugs. (
  • In vitro transient transcription, glutathione S -transferase pull-down assays, and mammalian one-hybrid and two-hybrid systems were used to explore drug-receptor interactions. (
  • Additionally, CYP3A family members are transcriptionally regulated by structurally diverse xenobiotics that in turn affect xenobiotic drug metabolism or other P 450-dependent drug-drug interactions ( 8 - 11 ). (
  • Drug-drug interactions with regard to paclitaxel therapy can occur by the direct inhibition of the activities of CYP450 enzymes. (
  • Drug-drug interactions occur at the level of PXR, where xenobiotics can function as activating agonists (e.g., the hyperforin constituent of St. John's wort) and induce the metabolism of paclitaxel, thereby significantly lowering its blood levels and therapeutic efficacy ( 17 ). (
  • Xenobiotic metabolism phase I II III, Cytochrome P450, Drug interactions, Drug design, Drug metabolising enzyme induction inhibition, Drug metabolism and pathologic conditions. (
  • Eleni A. Rekka*, Panos N. Kourounakis and Maria Pantelidou, "Xenobiotic Metabolising Enzymes: Impact on Pathologic Conditions, Drug Interactions and Drug Design", Current Topics in Medicinal Chemistry (2019) 19: 276. (
  • This dynamic gut ecosystem consists of many unique features, such as microniches, pH gradients, and dynamic microbe-tissue interactions of relevance for microbial biotransformations. (
  • Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes. (
  • Individual case reports provide evidence that interactions do occur between hypericum and other drugs, but these are rare. (
  • The overview is a logical extension from existing reports by focusing attention to the frequency of adverse effects, a point that is particularly relevant in light of the potential for adverse drug interactions with hypericum use. (
  • Part III: Drug Interactions. (
  • 19. Clinical Drug-Drug Interactions. (
  • Phase II enzymes have attracted much less attention in clinical pharmacology than cytochromes P450 because drug interactions involving these enzymes are relatively Fig. 1. (
  • Drug metabolism and drug interactions: effort and clinical value of in vitro models generic xenical 60 mg otc. (
  • In vitro cytochrome P450 inhi- bition facts and the prognosis of drug-drug interactions: qualitative relationships generic 60mg xenical with mastercard, quantitative predictions 60 mg xenical overnight delivery, and the rank-order nearer buy discount xenical 120 mg line. (
  • The utility of in vitro cytochrome P450 inhibition statistics in the forecast of drug-drug interactions buy generic toradol 10 mg online . (
  • Database analyses object of the forecast of in vivo drug- drug interactions from in vitro observations. (
  • Predicting inhibitory drug-drug interactions and evalu- ating cure-all interaction reports using defence mechanism constants. (
  • Drug-drug interactions is one of the major determinant in drug development and clinical applications. (
  • During treatment of tuberculosis and human immunodeficiency virus (HIV) coinfections, a combination of multiple therapeutic drugs is used, which is potential for interactions between coadministered drugs. (
  • Overall, this study will be helpful to understand the drug-interactions between the ARV or anti-TB drug regimen or with concomitantly used drugs at a glance. (
  • By understanding the unique functions and characteristics of enzymes and transporters, it may use in the management of drug interactions in the treatment of HIV and TB. (
  • To date, it is very common to alteration of drug's clinical response in multiple drug regimen by another drug is defined as a drug-drug interactions (DDI). (
  • This review evaluates the major human hepatic drug-metabolizing CYP enzymes and their clinically relevant substrates, inhibitors, and inducers. (
  • The cytochrome P450 superfamily of enzymes plays a major role in the biotransformation of most xenobiotics as well as in the metabolism of important endogenous substrates such as steroids and fatty acids. (
  • Human cytosolic sulphotransferase (SULT) enzymes catalyse the sulphate conjugation of many exogenous substrates, such as drugs and some xenobiotics, but also endogenous substrates, such as thyroid hormones 1 and neurotransmitters. (
  • Members of the cytochrome P450 (CYP) gene superfamily encode for heme proteins involved in the oxidative metabolism of xenobiotic and endogenous substrates in all species ( 1 ). (
  • Presented here are recent advances in biochemical, toxicological, and regulatory aspects of oxidative drug metabolizing enzymes. (
  • The present study sought to evaluate the association of genetic polymorphisms in xenobiotic-metabolizing enzymes with hematological and biochemical profiles. (
  • Biochemical sulphation is part of the phase II detoxification metabolism in humans. (
  • Biochemical reaction network modeling: predicting metabolism of organic chemical mixtures. (
  • These findings suggest that activation of hPXR with selective displacement of corepressors is an important mechanism by which microtubule-stabilizing drugs induce drug-metabolizing enzymes both in vitro and in vivo . (
  • Similarly, a puddle of in vitro cultured cells or even a purified enzyme solution may act on a chemical, and that would be called biotransformation because a biological system was involved, even if it were totally separated form any actual living organism. (
  • Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection , Curr Top Med Chem. (
  • The effect of feeding piglets with the diet containing green tea extracts or coumarin on in vitro metabolism of aflatoxin B1 by their tissues. (
  • Primary hepatocytes and their cultures are a simple but versatile, well-controlled, and relatively easy to handle in vitro system that is well-accepted for investigating xenobiotic biotransformation, enzyme induction and inhibition, and (biotransformation-mediated) hepatotoxicity. (
  • We carried out in vitro drug metabolism assays to pin-point the enzyme responsible for TETA metabolism. (
  • These findings should prove useful for in vitro and pre-clinical studies of cancer metabolism, and aid the optimization of metabolism-based cancer therapies and diagnostics. (
  • This approach intrinsically distinguishes drug- and system specific parameters explicitly, allowing accurate extrapolation from in vitro to in vivo and across species. (
  • This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. (
  • The use of full-grown human hepatocytes in primary learning and other in vitro systems to study drug metabolism in man. (
  • To date, drug-metabolizing enzymes mediated DDIs have been extensively studied in vitro as well as in vivo , emerging understanding has led to uptake and efflux transporters being recognized as a significant determinant of drug disposition that may cause significant DDIs. (
  • The CYP2E1 is an enzyme responsible for the metabolism of xenobiotics, including toxic and therapeutic agents, and is involved in oxidative bioactivation of hydrophobic chemicals, such as benzene and acrylamide. (
  • As predicted, due to its high perfusion, zone I plays a large role in oxidative metabolisms such as beta-oxidation, gluconeogenesis, bile formation, cholesterol formation, and amino acid catabolism. (
  • P450s localised in mitochondria have recently been shown to contribute to the neurotoxicity of some drugs and can lead to oxidative damage to mitochondria, possibly contributing to the development of neurodegenerative diseases. (
  • On the other hand, drug metabolizing enzymes comprising of the Phase I oxidative enzymes (cytochrome-P-450s, CYPs) and the conjugation Phase II enzymes (sulfotransferases, glucuronyl transferases, N -acetyltransferases and glutathione-S-transferases), are key players in exogenous/ endogenous compound and drug metabolism, and are differentially expressed in various mammalian tissues. (
  • Because induction of drug efflux transporters is one of the major underlying mechanisms of drug resistance in cancer chemotherapy, and human pregnane X receptor (hPXR) is one of the principal "xenobiotic" receptors whose activation induces transporter and drug-metabolizing enzyme gene transcription, it would be ideal to develop chemotherapy drugs that do not activate hPXR. (
  • These mechanisms may also be relevant to the regulation of hPXR by other xenobiotics and drugs ( 8 , 18 ). (
  • Several other drug-resistance mechanisms in H. contortus have been described, with one of these based on increased deactivation and/or efflux of anthelmintics via the increased expression of drug-metabolizing enzymes. (
  • Investigating the temporal behavior of molecular events has been an important subject to understand the underlying mechanisms governing the biological system in response to, such as, drug treatment. (
  • Namandjé began her independent research career in 2010 as an assistant professor of Medicine and Pharmacology & Molecular Sciences at The Johns Hopkins University School of Medicine where her initial work investigating the mechanisms of anti-HIV drug-induced toxicities was supported by a PhRMA Foundation Research Starter Grant. (
  • Xenobiotic biotransformation mechanisms are critical for inactivation and disposal of both externally-ingested drugs as well as endogenous substances. (
  • 1 Detoxification Mechanisms in Fish -Regulation and Function of Biotransformation and Efflux in Fish Exposed to Pharmaceuticals and Other Pollutants Britt Wassmur Akademisk avhandling för filosofie doktorsexamen i zoofysiologi, som med tillstånd från Naturvetenskapliga fakulteten kommer att offentligt försvaras fredagen den 16 november 2012 kl i föreläsningssalen, Zoologihuset, Institutionen för biologi och miljövetenskap, Medicinaregatan 18 A, Göteborg. (
  • Molecular mechanisms of cytochrome P-450 induction at hand xenobiotics: an expanded role for atomic hormone receptors. (
  • Drug candidates that are extensively excreted into bile may never achieve adequate concentrations in vivo. (
  • Loss of righting reflex was used to assess effects of drugs on PXR activity in vivo . (
  • These drugs resulted in shortened duration of loss of righting reflex in vivo , indicating drug-induced activation of PXR in mice. (
  • The utility of CL-LCN mice for in vivo drug metabolism studies was explored using the cytochrome P450 (P450) prodrug cyclophosphamide (CPA). (
  • In vivo drug disposition is further influenced by the activities of drug transporters ( Ho and Kim, 2005 ) and other often complex physiological factors, such as organ perfusion rates and routes of drug delivery. (
  • In this respect, receptor theory constitutes the basis for 1) prediction of in vivo drug concentration-effect relationships and 2) characterization of target association-dissociation kinetics as determinants of hysteresis in the time course of the drug effect. (
  • UDP-glucuronosyltransferases (UGT) catalyze the biotransformation of many endobiotics and xenobiotics, and are coded by polymorphic genes. (
  • Xenobiotic metabolizing enzymes, important for the metabolism, elimination and detoxification of exogenous agents, are found in most tissues and organs and are distinguished into phase I and phase II enzymes, as well as phase III transporters. (
  • In its role as the primary eliminator of exogenous drugs and toxins, the kidney is vulnerable to develop various forms of injury. (
  • These transport proteins are primarily expressed in the apical membrane of epithelial cells, such as enterocytes, which are exposed to exogenous xenobiotics. (
  • As such, the term is generally used to refer to hepatic metabolism of drugs, but could in fact apply to various other settings. (
  • 2005 ) found that the loss of hepatic CPR expression caused a significant decrease, but not a total loss, of CPR- and P450-dependent CPA clearance, confirming that hepatic metabolism plays a major role in CPA disposition. (
  • This induces the expression of genes that regulate the 3 phases of biotransformation. (
  • The transcriptional activation of genes regulating biotransformation and transport by the liganded human nuclear xenobiotic receptor, PXR, was inhibited by the commonly used antifungal ketoconazole and related azole analogs. (
  • The nuclear xenobiotic receptor PXR and, to a lesser extent, other adopted orphan nuclear receptors (e.g., constitutive androstane receptor, CAR) control genes encoding drug-metabolizing enzymes and transporters at the level of transcription ( 11 , 12 ). (
  • In addition, hematological disorders may also be related to polymorphisms in genes encoding xenobiotic-metabolizing enzymes, such as cytochrome P4502E1 (CYP2E1), myeloperoxidase (MPO), NAD(P)H:quinone oxidoreductase 1 (NQO1), and glutathione S-transferase (GST) [ 3 - 6 ]. (
  • The highest density of bacteria is present in the large intestine, with recent estimates of 10 13 bacterial cells in the large intestine associated with microbial genes encoding a broad range of enzymes necessary for xenobiotic biotransformation. (
  • Ascorbic acid deficiency affects genes for oxidation-reduction and lipid metabolism in livers from SMP30/GNL knockout mice. (
  • Many recent epidemiologic investigations have examined associations between polymorphic genes that code for enzymes involved in xenobiotic biotransformation (i.e. metabolism) and disease and have generated interesting findings. (
  • 19 Often, CNPs and CNVs are associated with disease, and also with the evolution of the genome itself and have been observed for a number of genes encoding drug metabolising enzymes. (
  • This acronym is widely used in the pharmaceutical industry to describe the four main processes governing drug disposition. (
  • She currently serves on the Drug Metabolism and Disposition editorial board and is a regular member of the NIH Xenobiotic and Nutrient Disposition and Action study section. (
  • This study was the first to suggest that the disposition of a drug being used for HIV prevention may vary depending on whether it is administered orally or topically to mucosal tissues that are sites of sexually transmitted HIV infection. (
  • Usually xenobiotics are lipophilic, and if they do not undergo regular metabolism, they can be potentially harmful to exposed humans. (
  • MetaPrint2D is a tool for predicting the sites of a molecule that are most likely to undergo Phase I metabolism, based on their similarity to known sites of metabolism and sites that are known not to be metabolised. (
  • This page focusses onstructural changes that occur when drugs undergo biotransformation and its importance in drug design and medicinal chemistry.Here, we also talk aboutdrug metabolism and the essential factors that underpin this central discipline in medicine. (
  • Transient transcription assays of a luciferase reporter in the presence and absence of a GAL4-steroid and xenobiotic receptor (SXR) plasmid in HepG2 cells showed that these drugs activate hPXR. (
  • also known as steroid and xenobiotic receptor (SXR), PAR, NR1I2, or PRR], can regulate the transcription of CYP3A4 as well as the transcription of other phase I and II enzymes involved in xenobiotic metabolism ( 12 - 14 ). (
  • An increased anthelmintics inactivation via biotransformation belongs to a significant drug-resistance mechanism in H. contortus . (
  • One metabolite of tramadol, namely, O -desmethyl-tramadol (metabolite M1 2 ), is known to have a higher affinity for opioid receptors than the parent drug. (
  • The anthelmintic drug ABZ and its primary metabolite ABZSO biotransformation, tested in the juvenile stages, shows significant differences between susceptible and resistant strain. (
  • In general, anything that increases the rate of metabolism ( e.g. , enzyme induction ) of a pharmacologically active metabolite will decrease the duration and intensity of the drug action. (
  • 9. Approaches to Performing Metabolite Elucidation: One Key to Success in Drug Discovery and Development (Ala F. Nassar). (
  • The group leveraged this observation and systematically mutated CYP3A5 toward CYP3A4 using formation of this metabolite as an activity probe to identify residues in CYP3A5 that confer specificity with regard to maraviroc metabolism. (
  • In some cases,a parent drug may be inactive but is eventually converted to the active metabolite in the body. (
  • NIMS is suitable for monitoring drug exposure and metabolite biotransformation with essentially single cell resolution, and provides new spatial and functional dimensions to studies of cancer metabolism without the need for radiotracers or tissue extraction. (
  • Finally, in phase III, the conjugated xenobiotics may be further processed, before being recognised by efflux transporters and pumped out of cells. (
  • 6. Introduction to drug transporters (Louis Leung and Aram Oganesian). (
  • Consequently, we have shown that activated orphan nuclear receptors controlling drug metabolism may be inactivated by ketoconazole, a known inhibitor of CYP450 and UGT1A enzyme activity. (
  • Vitamin E, nuclear receptors and xenobiotic metabolism. (
  • Orphan nuclear receptors with no known endogenous ligands have been discovered to regulate drug-mediated induction of cytochromes P450 (CYP), the major drug-metabolizing enzymes. (
  • These results provide convincing evidence for a major role of CXR in the regulation of CYP2H1 and add a member to the family of xenobiotic-activated orphan nuclear receptors. (
  • A link between CYP regulation and nuclear receptors has been established with the discovery of the role of several orphan nuclear receptors in the induction of CYPs by xenobiotics. (
  • Tumoral Drug Metabolism: Perspectives and Therapeutic Implications. (
  • Genetic variation in the receptors and other intracellular targets that mediate the pharmacodynamic effects of drugs can affect therapeutic outcomes. (
  • The cytochromes P450 (CYPs) constitute a superfamily of hemoprotein enzymes that are responsible for the biotransformation of numerous xenobiotics, including therapeutic agents. (
  • Our observations may facilitate new strategies to improve the clinical efficacy of drugs and to reduce therapeutic side effects. (
  • The metabolism of cancer cells is different from the metabolism of normal cells, and these differences can be used to find targets for therapeutic intervention in cancer. (
  • The hepatic endoplasmic reticulum (ER)-anchored monotopic proteins, cytochromes P450 (P450s), are enzymes that metabolize endobiotics (physiologically active steroids and fatty acids), as well as xenobiotics including therapeutic/chemotherapeutic drugs, nutrients, carcinogens, and toxins. (
  • Because gp78/AMFR is not only an E3 Ub-ligase, but also a cell-surface prometastatic oncogene that is upregulated in various malignant cancers, our finding that hepatic gp78/AMFR knockout can enhance P450-dependent bioactivation of relevant cancer chemotherapeutic prodrugs is of therapeutic relevance and noteworthy in prospective drug design and development. (
  • On the other hand, drugs and toxicants could affect circadian clock gene expression to produce biological effects leading to therapeutic or toxic outcomes. (
  • Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. (
  • Recent molecular studies have shed light on the mechanism of how hypericum may interact with other therapeutic drugs. (
  • In addition, it is known that skeletal muscle may sequester some therapeutic drugs [2]. (
  • With the in-depth study of the physiological function and mechanism of action of noncoding RNA in recent years, making it gradually realized extensive regulation of non-coding RNA gene expression, which occurs in tumor development, invasion and metastasis, drug resistance and other processes plays an important role. (
  • Chicken hepatocytes and, more recently, chicken hepatoma cells have been used extensively as a model for elucidating the molecular mechanism of xenobiotic induction (for recent examples, see refs. (
  • Xenobiotic biotransformation is the principal mechanism for maintaining homeostasis during organism exposure to foreign molecules such as drugs. (
  • In translational drug research, mechanism-based PK-PD modeling has been recognized as a tool for bringing forward early insights in drug efficacy and safety into the clinical development. (
  • An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. (
  • Biotransformation is a major mechanism for drug elimination. (
  • Our phase I metabolism products include enzymes such as cytochrome P450s and related electron transport proteins, other oxidases, and a select list of related antibodies. (
  • EC is an alternative method to study drug metabolism and toxicities in early phases by mimicking phase I metabolism [ 7 , 8 , 9 , 10 ]. (
  • Because CYP450 isoenzymes mostly catalyse the first step of biotransformation, this function is called phase I metabolism. (
  • Phase I metabolism often, but not always, precedes diverse conjugation steps, also called phase II metabolism. (
  • The cytochromes P450 constitute a superfamily of heme enzymes responsible for the metabolism of xenobiotics and endobiotics. (
  • Cytochrome P450 (CYP) enzymes, consisting of several subfamilies and further divided into isoforms, are responsible for the metabolism of most drugs. (
  • The duration and intensity of pharmacological action of most lipophilic drugs are determined by the rate they are metabolized to inactive products. (
  • Drugs are lipophilic in nature. (
  • Point 1 Xenobiotic biotransformation or drug metabolism is the process of converting lipophilic (fat-soluble) chemicals, which are readily absorbed from the gastrointestinal tract and other sites, into hydrophilic (water-soluble) chemicals, which are readily excreted in urine or bile. (
  • Most small drug molecules are relatively lipophilic and in the body, they are modified or broken down such that they are readily more excretable. (
  • In addition, decreased drug lipophilicity limits a drug's capacity to redistribute and accumulate in highly lipophilic areas, such as fat or brain tissue. (
  • Indra R, Pompach P, Vavrova K, Jaklova K, Heger Z, Adam V, Eckschlager T, Kopeckova K, Arlt VM, Stiborova M: Cytochrome P450 and flavin-containing monooxygenase enzymes are resposible for differential oxidation of anti-thyroid-cancer drug vandetanib by human and rat hepatic microsomal systems. (
  • We observed an inverse relationship between oxidation potential and drug stability. (
  • 2 h) drug molecules to prospectively survey the relationship between oxidation potential and stability. (
  • The latter step has been called "phase III metabolism", 4 indicating the close connection to the oxidation and conjugation steps of detoxification. (
  • The mammalian enzymes involved in the hydrolysis, reduction, oxidation, and conjugation of xenobiotics are listed in Table 6-1 , together with their principal subcellular location. (
  • Biotransformation is also utilized in the metabolism of many prodrugs to their active form, for example enalapril to enalaprilate. (
  • These drugs are referred to as prodrugs . (
  • Corning provides cryopreserved primary human hepatocytes to support major applications in drug and xenobiotic biotransformation. (
  • Superior accommodating hepatocytes as a way for the valuation of structure-activity relationship in cytochrome P450 induction embryonic of xenobiotics: approximation of rifampin, rifapentine and rifabutin. (
  • The erratic toxicities of microtubule-binding anticancer drugs can be directly linked in part to the consequences of CYP450-directed drug biotransformation and transporter-dependent elimination ( 1 - 4 ). (
  • For other drugs belonging to this class, inducing or inhibiting either CYP450 or multidrug resistance-1 (MDR1) function has resulted in altered drug metabolism, leading to distinct pharmacokinetic and pharmacodynamic sequelae ( 6 - 8 ). (
  • When xenobiotics are introduced to the body (e.g., drug molecules) they encounter a variety of potential redox modulations, including cytochrome p450 (CYP450) enzymes. (
  • This starts the first phase of biotransformation which makes it more water soluble. (
  • Recognizing risk factors that increase renal vulnerability to drug-induced kidney disease is the first step in reducing the renal complications of drugs and toxins. (
  • When the drug turns polar it becomes more soluble in the extracellular fluid and thus more filterable in the renal tubules. (
  • Namandjé is a recipient of the 2014 Tanabe Young Investigator Award from the American College of Clinical Pharmacology and the 2015 Drug Metabolism Early Career Achievement Award from the American Society for Pharmacology and Experimental Therapeutics. (
  • Biotransformation means chemical alteration of chemicals such as nutrients, amino acids, toxins, and drugs in the body. (
  • A number of factors enhance the vulnerability of the kidney to the nephrotoxic effects of drugs and toxins. (
  • both contribute to bile formation by transport of drugs, toxins, and waste products across the canalicular membrane. (
  • This will lead to individual differences in bioavailability of different drugs, toxins, and (food derived) carcinogens. (
  • Detoxification of xenobiotics, including toxins, carcinogens, and drugs, is the central task of many metabolising enzymes in the body. (
  • The mammalian drug biotransformation systems are thought to have first evolved from the need to detoxify and eliminate plant and bacterial bioproducts and toxins, which later extended to drugs and other environmental xenobiotics. (
  • In the past two decades, designers of new drugs have employed the increasing body of knowledge of how drugs are absorbed, distributed, metabolized, and excretedthe ADME concept-to optimize drug efficacy. (
  • A classic example of differing pharmacogenetics and drug efficacy, is codeine. (
  • Metabolism of drugs is an important aspect of their efficacy after administration to the body. (
  • Pharmacokinetic-Pharmacodynamic (PK-PD) modeling helps to better understand drug efficacy and safety and has, therefore, become a powerful tool in the learning-confirming cycles of drug-development. (
  • In short, 'metabolism of drugs' is a form of biotransformation which happens to drugs in a body, whereas 'biotransformation' is a more general term which applies equally well to the actions of a disembodied enzyme digesting an oil slick. (
  • Cayman scientists are experts in the Synthesis, Purification, and Characterization of Biochemicals ranging from small drug-like Heterocycles to complex Biolipids, Fatty Acids, and many others. (
  • For example, the rate of metabolism determines the duration and intensity of a drug's pharmacologic action. (
  • There is a huge inter-individual difference in the rate of metabolism in microsome and cytosol (K m range 181 - 12,457 μM, V max range 110 - 3,068 pg/min/mg protein). (
  • The altered cellular responsiveness was observed when drugs were assayed at sub- and low-micromolar concentrations, suggesting that suppressed expression of carboxylesterases by IL-6 has profound pharmacological consequences, particularly with those that are hydrolyzed in an isoform-specific manner. (
  • Its rate is an important determinant of the duration and intensity of the pharmacological action of drugs. (
  • FDA requires that pharmacological properties of any drug metabolized via acetylation route have to be investigated in population with different NAT2 phenotype. (
  • Relation of induction of benign drug-metabolizing enzymes: pharmacological and toxicological implications. (
  • In actual fact the college past papers have never included any reference to biotransformation in its broadest definition, and only one mention of hepatic clearance processes (in Question 20 from the first paper of 2016). (
  • It actually seems reasonable to use the terms synonymously, even though the term 'metabolism' should really be reserved for nutritive processes. (
  • Our research is leading to the development of more sustainable, environmentally friendly, chemical processes to accelerate drug development and improve the safety of medicines. (
  • These models differ from descriptive PK-PD models in that they quantitatively characterize specific processes in the causal chain between drug administration and effect. (
  • Drug conjugate analysis focuses mainly on sample preparation, hydrolysis, derivitization, and subsequent analysis of glucuronide and sulfate conjugates. (
  • The term xenobiotic includes medicinal as well as environmental and agricultural chemicals and macromolecules. (
  • Other commonly used organic chemicals are also drugs, and are metabolized by the same enzymes as drugs. (
  • Biological systems evolve transiently or sustainably according to sequential time points after perturbation by environment insults, drugs and chemicals. (
  • A variety of drugs, steroids, and chemicals activate CXR in CV-1 monkey cell transactivation assays. (
  • These data show that a range of CYP enzymes are expressed in the skeletal muscle of children and adolescents, suggesting that the metabolism of several xenobiotic chemicals to which humans are exposed takes place in muscle cells. (
  • Moreover P450s are involved in the synthesis and degradation of important endogenous chemicals, physiological roles which can be affected by drugs and dietary chemicals. (
  • Historical development of human environmentrelations, distribution and fate of chemicals in the environment, their toxic potentials, epidemiological findings, biomagnification and toxicokinetics of xenobiotics in the environment. (
  • This gene encodes a member of the cytochrome P450 superfamily of enzymes, which participate in drug metabolism and the synthesis of cholesterol, steroids and other lipids. (
  • Cytochrome P450 enzymes (CYPs, P450s) especially those responsible for drug metabolism in humans, are the unifying theme of the research in our lab. (
  • Notable examples include nerve damage among individuals homozygous for some variants of the N-acetyltransferase 2 gene ("slow acetylators") given isoniazid as an antituberculosis therapy, hemolytic anemia among glucose 6-phosphate dehydrogenase-deficient patients given aminoquinoline antimalarial drugs, and varied rates of biotransformation of debrisoquine, an antihypertensive drug, due to genetic variation at the CYP2D6 locus. (
  • Genetic and environmental cues, including stresses from anti-cancer treatments, can induce significant changes in cell and tissue metabolism. (
  • The enzymes of xenobiotic metabolism, particularly the glutathione S-transferases are also important in agriculture, since they may produce resistance to pesticides and herbicides. (
  • Phase II metabolism in human skin: skin explants show full coverage for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. (
  • Accepted: April 20, 2010 Key words: Phase II biotransformation/udp-glucuronosyltransferases/sulfotransferases, -acetyltransferases/glutathione S-transferases/Thiopurine S-methyl transferase/catechol -methyl transferase Background. (
  • Drug metabolism is divided into three phases. (
  • The metabolism of drugs is often divided into two phases, biotransformation and bioconjugation, respectively. (
  • In general, biotransformation is conducted in two phases, where the CYPs belonging to family 1-3 are part of phase I, usually adding reactive groups to the parent compound. (
  • ITRDUCTI It is generally accepted that the biotransformation of substances foreign to the body (xenobiotics) including drugs is divided into phases I and II. (
  • Drug metabolism can result in toxication or detoxication - the activation or deactivation of the chemical. (
  • The official journal of the International Society for the Study of Xenobiotics, Drug Metabolism Reviews provides the most rapid publication of drug metabolism research in the field. (
  • She is a member of the American Society for Pharmacology and ExperimentalTherapeutics and the International Society for the Study of Xenobiotics (ISSX) and is currentlyserving on the Editorial Board of Drug Metabolism Reviews. (
  • A balance between Phase I and II enzymes is generally necessary to promote the efficient detoxification and elimination of xenobiotics, thereby protecting the body from injury caused by exposure. (
  • This book will be an important handbook and desk reference for pharmacologists, toxicologists, clinical scientists, and students interested in the fields of pharmacology, biochemistry, and drug metabolism. (
  • Here, we report the cloning of an orphan nuclear receptor from chicken, termed chicken xenobiotic receptor (CXR), that is closely related to two mammalian xenobiotic-activated receptors, the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). (
  • The classes of pharmaceutical drugs that utilize this method for their metabolism include phenothiazines, paracetamol , and steroids. (
  • Our portfolio of drug transport-related products includes transporter protein/ membrane preparations as well as selected antibodies and modulators to transport proteins. (
  • Interplay of metabolizing enzymes and transporter of xenobiotics. (
  • Drug-induced kidney disease occurs primarily in patients with underlying risk factors. (
  • Drug redistribution from the primary site may also terminate the action, although this occurs infrequently. (
  • The metabolism of pharmaceutical drugs is an important aspect of pharmacology and medicine. (