Biotransformation: 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.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Cytochrome P-450 Enzyme System: 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.Pharmaceutical Preparations: 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.Microsomes, Liver: Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.Metabolic Detoxication, Drug: 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.Cytochrome P-450 CYP3A: 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.Aryl Hydrocarbon Hydroxylases: 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.Hexobarbital: A barbiturate that is effective as a hypnotic and sedative.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Pharmacokinetics: 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.Metabolic Detoxication, Phase II: 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.Glucuronosyltransferase: 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 2.4.1.17.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Metabolic Detoxication, Phase I: 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.Antipyrine: 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)Cunninghamella: A genus of zygomycetous fungi of the family Cunninghamellaceae, order MUCORALES. Some species cause systemic infections in humans.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Mixed Function Oxygenases: 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.Dealkylation: The removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Oxidoreductases, N-DemethylatingKetoconazole: Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.Phenobarbital: 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.Glutathione Transferase: 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.Receptors, Steroid: 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.Cytochrome P-450 CYP1A2: A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.Cytochrome P-450 CYP2D6: 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.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Umbelliferones: 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.Energy Metabolism: The chemical reactions involved in the production and utilization of various forms of energy in cells.Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug.Oxidation-Reduction: 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).Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Glucuronides: 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.Enzyme Induction: 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.Cytochrome P-450 CYP1A1: 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.Mass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.Oxygenases: Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Cytochrome P-450 CYP2E1: 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.Steroid 16-alpha-Hydroxylase: 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.Coumarins: Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.Kinetics: The rate dynamics in chemical or physical systems.Pharmacogenetics: A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION).Microsomes: 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)7-Alkoxycoumarin O-Dealkylase: 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.NADPH-Ferrihemoprotein Reductase: A flavoprotein that catalyzes the reduction of heme-thiolate-dependent monooxygenases and is part of the microsomal hydroxylating system. EC 1.6.2.4.Biodegradation, Environmental: Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.Molecular Structure: 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: 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.Steroid Hydroxylases: Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.Chromatography, Liquid: Chromatographic techniques in which the mobile phase is a liquid.Metabolic Clearance Rate: 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.Aminopyrine N-DemethylaseSpecies Specificity: 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.Stereoisomerism: 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)Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Environmental Pollutants: 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.Receptors, Cytoplasmic and Nuclear: 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.Aminopyrine: 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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Rats, Sprague-Dawley: 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.Dextromethorphan: 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.P-Glycoprotein: 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).Arylamine N-Acetyltransferase: 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.beta-Naphthoflavone: A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)Cytochromes b5: 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.Aniline Hydroxylase: 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.-.Magnetic Resonance Spectroscopy: 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).Acetaminophen: 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.Gas Chromatography-Mass Spectrometry: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.Glutathione: 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, Messenger: 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.Carbon Radioisotopes: Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes.Hydrocarbons, HalogenatedMidazolam: 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.Tissue Distribution: 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.Polymorphism, Genetic: 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.Methylcholanthrene: A carcinogen that is often used in experimental cancer studies.Molecular Sequence Data: 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.Tandem Mass Spectrometry: 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.Trichloroethanes: 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.Bile: 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.Drug Evaluation, Preclinical: Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications.Glucuronates: 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.Administration, Oral: The giving of drugs, chemicals, or other substances by mouth.Safety-Based Drug Withdrawals: 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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Biological Transport: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Models, Biological: 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.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Cytochrome P-450 CYP2B1: 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.Drug-Related Side Effects and Adverse Reactions: 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.Ethylmorphine-N-Demethylase: 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.Metabolism: 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.Biological Availability: 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.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Safrole: 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).Drug-Induced Liver Injury: 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.Sulfotransferases: 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.NAD(P)H Dehydrogenase (Quinone): 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.Receptors, Aryl Hydrocarbon: 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.Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic.Macaca fascicularis: 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.Trinitrotoluene: A 2,4,6-trinitrotoluene, which is an explosive chemical that can cause skin irritation and other toxic consequences.Methaqualone: 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)Recombinant Proteins: Proteins prepared by recombinant DNA technology.Carboxylic Ester Hydrolases: Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.Glucose: 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, Cultured: 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.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Arylsulfotransferase: 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 2.8.2.1.Oxidoreductases: 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)Metabolic Networks and Pathways: Complex sets of enzymatic reactions connected to each other via their product and substrate metabolites.Rats, Inbred F344Rats, Inbred Strains: 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.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Amobarbital: 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)Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)Polychlorinated Biphenyls: 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.Phenols: Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.Sydnones: OXADIAZOLES bearing an oxygen at the 5-position. They are mesoionic, with delocalized positive and negative charges.Debrisoquin: 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.Reverse Transcriptase Polymerase Chain Reaction: 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.Bile Acids and Salts: 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.Water Pollutants, Chemical: Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water.Troleandomycin: A macrolide antibiotic that is similar to ERYTHROMYCIN.Epoxide Hydrolases: Enzymes that catalyze reversibly the formation of an epoxide or arene oxide from a glycol or aromatic diol, respectively.Testosterone: 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.Dogs: 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)Dinitrochlorobenzene: 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.Atrazine: 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)Quantitative Structure-Activity Relationship: 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.Gordonia Bacterium: 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.Triazines: 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.Gene Expression Regulation: 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.Benzo(a)pyrene: 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.Mephenytoin: An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Serial Publications: 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)Amino Acid Sequence: 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.Area Under Curve: 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)Carcinogens: 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.Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural applications, on wood, plastics, or other materials, in swimming pools, etc.Phenylbutazone: A butyl-diphenyl-pyrazolidinedione that has anti-inflammatory, antipyretic, and analgesic activities. It has been used in ANKYLOSING SPONDYLITIS; RHEUMATOID ARTHRITIS; and REACTIVE ARTHRITIS.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Mice, Inbred C57BLIsoflavones: 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.Sparteine: 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.Chlorobutanol: 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.Intestine, Small: 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.Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE.Hydrocarbons, Chlorinated: Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Oncorhynchus kisutch: 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.Methoxyflurane: 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)Blotting, Western: 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.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Toluene: A widely used industrial solvent.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Toxicology: The science concerned with the detection, chemical composition, and biological action of toxic substances or poisons and the treatment and prevention of toxic manifestations.Oligonucleotide Array Sequence Analysis: 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.Equol: A non-steroidal ESTROGEN generated when soybean products are metabolized by certain bacteria in the intestines.Aminoethylphosphonic Acid: An organophosphorus compound isolated from human and animal tissues.ATP-Binding Cassette Transporters: 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.Estrogens, Non-Steroidal: Non-steroidal compounds with estrogenic activity.Phenytoin: 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.Liver, Artificial: Devices for simulating the activities of the liver. They often consist of a hybrid between both biological and artificial materials.Membrane Transport Proteins: 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, Pharmaceutical: Societies whose membership is limited to pharmacists.Multidrug Resistance-Associated Proteins: 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.Chlorzoxazone: 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)Monoterpenes: 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).Toxicity Tests: 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.DNA, Complementary: 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.Biocatalysis: The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.NADP: 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)Protein Binding: 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.Caco-2 Cells: 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, Thin Layer: 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)Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Nitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.Pregnenolone Carbonitrile: 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.Plant Extracts: 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.Sex Characteristics: 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.Polycyclic Hydrocarbons, Aromatic: 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)Spectrometry, Mass, Electrospray Ionization: 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.Insecticides: 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.Mice, Knockout: 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.Porphyrinogens: Colorless reduced precursors of porphyrins in which the pyrrole rings are linked by methylene (-CH2-) bridges.Cell Line, Tumor: A cell line derived from cultured tumor cells.P-Glycoproteins: 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.Rifampin: 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)
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 ...
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 ...
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 ...
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 ...
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 ...
Xenobiotics such as synthetic drugs, natural poisons and antibiotics are detoxified by a set of xenobiotic-metabolizing enzymes ... Galvão T, Mohn W, de Lorenzo V (2005). "Exploring the microbial biodegradation and biotransformation gene pool". Trends ... Respirometry Stream metabolism Sulfur metabolism Thermic effect of food Urban metabolism Water metabolism Overflow metabolism ... Danielson P (2002). "The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans". Curr Drug Metab. ...
The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm. 2008;363(1-2):1-25. doi:10.1016/j. ... Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res. 2013;69(1):21-31. doi:10.1016/j.phrs.2012.07.009. Saad R ... The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm. 2008;363(1-2):1-25. doi:10.1016/j. ... The gastrointestinal microbiota as a site for the biotransformation of drugs. Int J Pharm. 2008;363(1-2):1-25. doi:10.1016/j. ...
For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body ... Those so far identified are generally involved in either biotransformation of xenobiotic compounds (e.g. CYP105A1 from ... CYPs are the major enzymes involved in drug metabolism, accounting for about 75% of the total metabolism. Most drugs undergo ... evolution and drug metabolism in humans". Current Drug Metabolism. 3 (6): 561-97. doi:10.2174/1389200023337054. PMID 12369887. ...
... 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 ( ...
... metabolism + excretion of the drugs. The resulting decrease of the drug's plasma concentration follows a biphasic pattern (see ... 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 and elimination. Variable volume pharmacokinetic models can be drug centered models that imply a volume of drug ...
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. PMID ... 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 ...
Decker M, Arand M, Cronin A (2009). "Mammalian epoxide hydrolases in xenobiotic metabolism and signalling". Arch. Toxicol. 83 ( ... 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 ...
... 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 ... Two classes of drugs target the mevalonate pathway: statins, which are used to reduce elevated cholesterol levels,[citation ...
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 ...
... 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. {\ ...
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 xenobiotic such as drugs, phytochemicals, and food toxicants ... "The gastrointestinal microbiota as a site for the biotransformation of drugs." International journal of pharmaceutics 363, no. ... IPA metabolism diagram "3-Indolepropionic acid". Human Metabolome Database. University of Alberta. Retrieved 12 October 2015. ...
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. ...
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 ...
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.. ...
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 ...
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 ...
... 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 ...
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 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 ...
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 ...
Chronic inflammation blocks xenobiotic and drug metabolism via inhibition of PXR(1). ... herbisarium.wordpress.com/2016/02/15/xenobiotics-and-biotransformation/. 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 ...
... 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 ...
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 ...
1994), who systematically characterized the major P450s involved in the biotransformation of drugs and other xenobiotics. Using ... substantiates the proximal small intestine as a major site for presystemic drug metabolism, as well as for drug-drug and drug- ... Wilkinson GR (2005) Drug metabolism and variability among patients in drug response. N Engl J Med 352: 2211-2221. ... and xenobiotics, the latter including a myriad of widely prescribed drugs. In humans, approximately 80% of oxidative metabolism ...
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 ...
P450s are oxidative metabolic enzymes that play critical roles in the biotransformation of endogenous compounds and xenobiotics ... 2008) The ontogeny of drug metabolism enzymes and implications for adverse drug events. Pharmacol Ther 118:250-267. ... The P450 2C subfamily is responsible for the metabolism of ∼30% of all clinical drugs in adults. We focused on two 2C enzymes ... play a pivotal role in not only the disposition and efficacy of therapeutic drugs but also the metabolism of other xenobiotics ...
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 ...
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 ...
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 ...
"Investigation of xenobiotics metabolism, genotoxicity, and carcinogenicity using Cyp2e1(−/−) mice," Current Drug Metabolism, ... humans exhibit mechanisms responsible for enzymatic metabolism or biotransformation of xenobiotics. This involves the ... and drugs. Usually xenobiotics are lipophilic, and if they do not undergo regular metabolism, they can be potentially harmful ... P. Sherratt and J. Hayes, Glutathione S-Transferases in Enzyme Systems that Metabolise Drugs and Other Xenobiotics Ioannides C ...
... has been developed to enumerate all metabolites and to predict the major ones of the given drugs or other xenobiotics. The ... Compounds foreign to an organisms normal biochemistry are metabolized by enzymatically catalysed biotransformations. That ... results can be influenced by the replacement or the modification of the biotransformation libraries used. The prediction model ...
  • 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. (deepdyve.com)
  • Phenobarbital (PB) and other drugs of this class of prototypical inducers display a distinct activation pattern of CYPs. (pnas.org)
  • 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. (pnas.org)
  • However, several CYPs contribute to drug metabolism in extrahepatic tissues as small intestine, colon, respiratory tract, or skin, which are organs directly in contact with xenobiotics [7, (scirp.org)
  • 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. (bsmiab.org)
  • 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). (derangedphysiology.com)
  • Drug conjugate analysis focuses mainly on sample preparation, hydrolysis, derivitization, and subsequent analysis of glucuronide and sulfate conjugates. (sigmaaldrich.com)
  • 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. (mhmedical.com)
  • 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. (cdc.gov)
  • 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. (sigmaaldrich.com)
  • 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. (alliedacademies.org)
  • Consequently, the expression profile of metabolizing enzymes in the muscle tissue may play a major role in drug myotoxicity. (scirp.org)
  • FLT-MP accumulation in xenograft tumors was shown to be sensitive to Docetaxel treatment, and TK1 immunoreactivity co-localized with tumor-specific antigens in xenograft tumors, supporting a role for xenograft-derived TK1 activity in tumor FLT metabolism. (biomedcentral.com)
  • Our portfolio of drug transport-related products includes transporter protein/ membrane preparations as well as selected antibodies and modulators to transport proteins. (sigmaaldrich.com)
  • These transport proteins are primarily expressed in the apical membrane of epithelial cells, such as enterocytes, which are exposed to exogenous xenobiotics. (bmj.com)
  • The three main purposes of metabolism are the conversion of food/fuel to energy to run cellular processes, the conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates, and the elimination of nitrogenous wastes. (wikipedia.org)
  • Metabolism is usually divided into two categories: catabolism, the breaking down of organic matter for example, the breaking down of glucose to pyruvate, by cellular respiration, and anabolism, the building up of components of cells such as proteins and nucleic acids. (wikipedia.org)
  • We are using artificial (or directed) evolution to engineer enzymes that are more efficient, robust and specialized than naturally occurring enzymes with the aim of selecting for properties that are commercially useful in the areas of drug discovery and development and bioremediation of pollutants in the environment. (edu.au)
  • Phase II metabolism is mediated by several different enzymatic systems, the most important being the UDP glucuronosyltransferases. (bmj.com)