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 family of steroids from which the androgens are derived.
Steroids that contain a ketone group at position 17.
Stable iodine atoms that have the same atomic number as the element iodine, but differ in atomic weight. I-127 is the only naturally occurring stable iodine isotope.
The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.
Glucose in blood.
The administration of liquid medication, nutrient, or other fluid through some other route than the alimentary canal, usually over minutes or hours, either by gravity flow or often by infusion pumping.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
Maintenance of a constant blood glucose level by perfusion or infusion with glucose or insulin. It is used for the study of metabolic rates (e.g., in glucose, lipid, amino acid metabolism) at constant glucose concentration.
Injections made into a vein for therapeutic or experimental purposes.
Tritium is an isotope of hydrogen (specifically, hydrogen-3) that contains one proton and two neutrons in its nucleus, making it radioactive with a half-life of about 12.3 years, and is used in various applications including nuclear research, illumination, and dating techniques due to its low energy beta decay.
The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.
Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation.
The rate dynamics in chemical or physical systems.
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.
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.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
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 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511)
Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.
Elements of limited time intervals, contributing to particular results or situations.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
A non-specific host defense mechanism that removes MUCUS and other material from the LUNGS by ciliary and secretory activity of the tracheobronchial submucosal glands. It is measured in vivo as mucus transfer, ciliary beat frequency, and clearance of radioactive tracers.
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.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
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.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
An aldehyde oxidoreductase expressed predominantly in the LIVER; LUNGS; and KIDNEY. It catalyzes the oxidation of a variety of organic aldehydes and N-heterocyclic compounds to CARBOXYLIC ACIDS, and also oxidizes quinoline and pyridine derivatives. The enzyme utilizes molybdenum cofactor and FAD as cofactors.
A technetium imaging agent used in renal scintigraphy, computed tomography, lung ventilation imaging, gastrointestinal scintigraphy, and many other procedures which employ radionuclide imaging agents.
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.
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 removing of alkyl groups from a compound. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
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.
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)
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.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
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)
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.
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 major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.
The giving of drugs, chemicals, or other substances by mouth.
Mononuclear cells with pronounced phagocytic ability that are distributed extensively in lymphoid and other organs. It includes MACROPHAGES and their precursors; PHAGOCYTES; KUPFFER CELLS; HISTIOCYTES; DENDRITIC CELLS; LANGERHANS CELLS; and MICROGLIA. The term mononuclear phagocyte system has replaced the former reticuloendothelial system, which also included less active phagocytic cells such as fibroblasts and endothelial cells. (From Illustrated Dictionary of Immunology, 2d ed.)
The middle segment of proinsulin that is between the N-terminal B-chain and the C-terminal A-chain. It is a pancreatic peptide of about 31 residues, depending on the species. Upon proteolytic cleavage of proinsulin, equimolar INSULIN and C-peptide are released. C-peptide immunoassay has been used to assess pancreatic beta cell function in diabetic patients with circulating insulin antibodies or exogenous insulin. Half-life of C-peptide is 30 min, almost 8 times that of insulin.
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.
FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.
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.
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 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.
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.
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.
Chemical substances having a specific regulatory effect on the activity of a certain organ or organs. The term was originally applied to substances secreted by various ENDOCRINE GLANDS and transported in the bloodstream to the target organs. It is sometimes extended to include those substances that are not produced by the endocrine glands but that have similar effects.
The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.
Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)
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.

Accumulation of astaxanthin all-E, 9Z and 13Z geometrical isomers and 3 and 3' RS optical isomers in rainbow trout (Oncorhynchus mykiss) is selective. (1/3580)

Concentrations of all-E-, 9Z- and 13Z- geometrical and (3R,3'R), (3R, 3'S) and (3S,3'S) optical isomers of astaxanthin were determined in rainbow trout liver, gut tissues, kidney, skin and blood plasma to evaluate their body distribution. Two cold-pelleted diets containing predominantly all-E-astaxanthin (36.9 mg/kg astaxanthin, 97% all-E-, 0.4% 9Z-, 1.5% 13Z-astaxanthin, and 1.1% other isomers, respectively) or a mixture of all-E- and Z-astaxanthins (35.4 mg/kg astaxanthin, 64% all-E-, 18.7% 9Z-, 12.3% 13Z-astaxanthin, and 2.0% other isomers, respectively), were fed to duplicate groups of trout for 69 d. Individual E/Z isomers were identified by VIS- and 1H-NMR-spectrometry, and quantified by high-performance liquid chromatography. Significantly higher total carotenoid concentration was observed in plasma of trout fed diets with all-E-astaxanthin (P < 0.05). The relative E/Z-isomer concentrations of plasma, skin and kidney were not significantly different among groups, whereas all-E-astaxanthin was higher in intestinal tissues and 13Z-astaxanthin was lower in liver of trout fed all-E-astaxanthin (P < 0.05). The relative amount of hepatic 13Z-astaxanthin (39-49% of total astaxanthin) was higher than in all other samples (P < 0.05). Synthetic, optically inactive astaxanthin was used in all experiments, and the determined dietary ratio between the 3R,3'R:3R, 3'S (meso):3S,3'S optical isomers was 25.3:49.6:25.1. The distribution of R/S-astaxanthin isomers in feces, blood, liver and fillet was similar to that in the diets. The ratio between (3S,3'S)- and (3R,3'R)-astaxanthin in the skin and posterior kidney was ca. 2:1 and 3:1, respectively, regardless of dietary E/Z-astaxanthin composition. The results show that geometrical and optical isomers of astaxanthin are distributed selectively in different tissues of rainbow trout.  (+info)

Absorption, metabolism, and excretion of 14C-temozolomide following oral administration to patients with advanced cancer. (2/3580)

The purpose of this study is to characterize the absorption, metabolism, and excretion of carbon 14-labeled temozolomide (14C-TMZ) administered p.o. to adult patients with advanced solid malignancies. On day 1 of cycle 1, six patients received a single oral 200-mg dose of 14C-TMZ (70.2 microCi). Whole blood, plasma, urine, and feces were collected from days 1-8 and on day 14 of cycle 1. Total radioactivity was measured in all samples. TMZ, 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) concentrations were determined in plasma, and urine and plasma samples were profiled for metabolite/degradation products. Maximum TMZ plasma concentrations were achieved between 0.33 to 2 h (mean, 1.2 h), and half-life, apparent volume of distribution, and oral clearance values averaged 1.9 h, 17 liters/m2, and 104 ml/min/m2, respectively. A first-order absorption, one-compartment linear model, which included first-order formation of MTIC from TMZ and elimination of MTIC via degradation to AIC, and a peripheral distribution compartment for AIC, adequately described the plasma TMZ, MTIC, and AIC concentrations. MTIC systemic clearance was estimated to be 5384 ml/min/m2, and the half-life was calculated to be 2.5 min. Metabolite profiles of plasma at 1 and 4 h after treatment showed that 14C-derived radioactivity was primarily associated with TMZ, and a smaller amount was attributed to AIC. Profiles of urine samples from 0-24 h revealed that 14C-TMZ-derived urinary radioactivity was primarily associated with unchanged drug (5.6%), AIC (12%), or 3-methyl-2,3-dihydro-4-oxoimidazo[5,1-d]tetrazine-8-carboxyl ic acid (2.3%). The recovered radioactive dose (39%) was principally eliminated in the urine (38%), and a small amount (0.8%) was excreted in the feces. TMZ exhibits rapid oral absorption and high systemic availability. The primary elimination pathway for TMZ is by pH-dependent degradation to MTIC and further degradation to AIC. Incomplete recovery of radioactivity may be explained by the incorporation of AIC into nucleic acids.  (+info)

Bioavailability and toxicity after oral administration of m-iodobenzylguanidine (MIBG). (3/3580)

meta-iodobenzylguanidine (MIBG) radiolabelled with iodine-131 is used for diagnosis and treatment of neuroadrenergic neoplasms such as phaeochromocytoma and neuroblastoma. In addition, non-radiolabelled MIBG, administered i.v., is used in several clinical studies. These include palliation of the carcinoid syndrome, in which MIBG proved to be effective in 60% of the patients. Oral MIBG administration might be convenient to maintain palliation and possibly improve the percentage of responders. We have, therefore, investigated the feasibility of oral administration of MIBG in an animal model. Orally administered MIBG demonstrated a bioavailability of 59%, with a maximal tolerated dose of 60 mg kg(-1). The first and only toxicity encountered was a decrease in renal function, measured by a reduced clearance of [51Cr]EDTA and accompanied by histological tubular damage. Repeated MIBG administration of 40 mg kg(-1) for 5 sequential days or of 20 mg kg(-1) for two courses of 5 sequential days with a 2-day interval did not affect renal clearance and was not accompanied by histological abnormalities in kidney, stomach, intestines, liver, heart, lungs, thymus, salivary glands and testes. Because of a sufficient bioavailability in absence of gastrointestinal toxicity, MIBG is considered suitable for further clinical investigation of repeated oral administration in patients.  (+info)

Phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. (4/3580)

We conducted a phase I and pharmacokinetic study of the topoisomerase II catalytic inhibitor fostriecin. Fostriecin was administered intravenously over 60 min on days 1-5 at 4-week intervals. Dose was escalated from 2 mg m(-2) day(-1) to 20 mg m(-2) day(-1) in 20 patients. Drug pharmacokinetics was analysed with high performance liquid chromatography with UV-detection. Plasma collected during drug administration was tested in vitro for growth inhibition of a teniposide-resistant small-cell lung cancer (SCLC) cell line. The predominant toxicities were elevated liver transaminases (maximum common toxicity criteria (CTC) grade 4) and serum creatinine (maximum CTC grade 2). These showed only a limited increase with increasing doses, often recovered during drug administration and were fully reversible. Duration of elevated alanine-amino transferase (ALT) was dose-limiting in one patient at 20 mg m(-2). Other frequent toxicities were grade 1-2 nausea/vomiting, fever and mild fatigue. Mean fostriecin plasma half-life was 0.36 h (initial; 95% CI, 0-0.76 h) and 1.51 h (terminal; 95% CI, 0.41-2.61 h). A metabolite, most probably dephosphorylated fostriecin, was detected in plasma and urine. No tumour responses were observed, but the plasma concentrations reached in the patients were insufficient to induce significant growth inhibition in vitro. The maximum tolerated dose (MTD) has not been reached, because drug supply was stopped at the 20 mg m(-2) dose level. However, further escalation seems possible and is warranted to achieve potentially effective drug levels. Fostriecin has a short plasma half-life and longer duration of infusion should be considered.  (+info)

Altered pharmacokinetics of a novel anticancer drug, UCN-01, caused by specific high affinity binding to alpha1-acid glycoprotein in humans. (5/3580)

The large species difference in the pharmacokinetics/pharmacodynamics of 7-hydroxystaurosporine (UCN-01) can be partially explained by the high affinity binding of UCN-01 to human alpha1-acid glycoprotein (AGP) (Fuse et al, Cancer Res., 58: 3248-3253, 1998). To confirm whether its binding to human AGP actually changes the in vivo pharmacokinetics, we have studied the alteration in its pharmacokinetics after simultaneous administration of human AGP to rats: (a) the protein binding of UCN-01 was evaluated by chasing its dissociation from proteins using dextran-coated charcoal. The UCN-01 remaining 0.1 h after adding dextran-coated charcoal to human plasma or AGP was approximately 80%, although the values for other specimens, except monkey plasma (approximately 20%), were <1%, indicating that the dissociation from human AGP was specifically slower than from other proteins; and (b) the pharmacokinetics of UCN-01 simultaneously administered with human AGP has been determined. The plasma concentrations after i.v. administration of UCN-O1 with equimolar human AGP were much higher than those after administration of UCN-01 alone. The steady-state distribution volume and the systemic clearance were reduced to about 1/100 and 1/200, respectively. Human AGP thus reduced the distribution and elimination of UCN-01 substantially. On the other hand, dog AGP, which has a low binding affinity for UCN-01, did not change the pharmacokinetics of UCN-01 so much. Furthermore, human AGP markedly reduced the hepatic extraction ratio of UCN-01 from 0.510 to 0.0326. Also, human AGP (10 microM) completely inhibited the initial uptake of UCN-01 (1 microM) into isolated rat hepatocytes, whereas the uptake of UCN-01 was unchanged in the presence of human serum albumin (10 microM). In conclusion, the high degree of binding of UCN-01 to human AGP causes a reduction in the distribution and clearance, resulting in high plasma concentrations in humans.  (+info)

L-Asparagine synthetase in serum as a marker for neoplasia. (6/3580)

L-Asparagine synthetase appears in serum approximately 7 days after the s.c. implantation of 1 X 10(5) cells of Leukemia 5178Y/AR (resistant to L-asparaginase) and increases in activity as the neoplasm grows and metastasizes. The principal source of the enzyme is the primary tumor. After intravranial inoculation of tumor, the rate of leakage of the enzyme is more pronounced than when the subcutaneous, intramuscular, or intraperitoneal routes are used. 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea (NSC 79037), a nitro-sourea effective in the palliation of L5178Y/AR, temporarily halts the influx of enzyme into the blood stream, as does surgical excision of the s.c. tumor nodules. Treatment of mice with L-asparaginase within 24 hr of inoculation of the tumor markedly augments both tumor growth and the rate of penetration of L-asparagine synthetase into the circulation. Several other L-asparagine synthetase into the circulation. Several other L-asparaginase-resistant tumors also were found to spill L-asparagine synthetase into the serum, but the correlation between this phenomenon and the specific activity of the enzyme in homogenates of the tumor was imperfect.  (+info)

Renal and metabolic clearance of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) during angiotensin-converting enzyme inhibition in humans. (7/3580)

We investigated the contributions of angiotensin-converting enzyme (ACE) and glomerular filtration to creating the new metabolic balance of the hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute and chronic ACE inhibition in healthy subjects. We also studied the effect of chronic renal failure on the plasma concentration of AcSDKP during long-term ACE inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8-fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE activity over time showed an intermittent reactivation of ACE between each captopril dose. In subjects with chronic renal failure (creatinine clearance<60 mL/min per 1.73 m2), plasma AcSDKP levels were 22 times higher (95% confidence interval, 15 to 33) in the ACEI group (n=35) than the control group (n=23); in subjects with normal renal function, they were only 4.1 times higher (95% confidence interval, 3.2 to 5.3) in the ACEI group (n=19) than the non-ACEI group (n=21). Renal failure itself led to a slight increase in plasma AcSDKP concentration. In conclusion, intermittent reactivation of ACE between doses of an ACEI is the major mechanism accounting for the lack of major AcSDKP accumulation during chronic ACE inhibition in subjects with normal renal function.  (+info)

Pharmacokinetics of beta-L-2',3'-dideoxy-5-fluorocytidine in rhesus monkeys. (8/3580)

beta-L-2',3'-Dideoxy-5-fluorocytidine (beta-L-FddC), a novel cytidine analog with an unnatural beta-L sugar configuration, has been demonstrated by our group and others to exhibit highly selective in vitro activity against human immunodeficiency virus types 1 and 2 and hepatitis B virus. This encouraging in vitro antiviral activity prompted us to assess its pharmacokinetics in rhesus monkeys. Three monkeys were administered an intravenous dose of [3H] beta-L-FddC at 5 mg/kg of body weight. Following a 3-month washout period, an equivalent oral dose was administered. Plasma and urine samples were collected at various times for up to 24 h after dosing, and drug levels were quantitated by high-pressure liquid chromatography. Pharmacokinetic parameters were obtained on the basis of a two-compartment open model with a first-order elimination from the central compartment. After intravenous administration, the mean peak concentration in plasma (Cmax) was 29.8 +/- 10.5 microM. Total clearance, steady-state volume of distribution, terminal-phase plasma half-life (t1/2 beta), and mean residence time were 0.7 +/- 0.1 liters/h/kg, 1.3 +/- 0.1 liters/kg, 1.8 +/- 0.2 h, and 1.9 +/- 0.2 h, respectively. Approximately 47% +/- 16% of the intravenously administered radioactivity was recovered in the urine as the unchanged drug with no apparent metabolites. beta-L-FddC exhibited a Cmax of 3.2 microM after oral administration, with a time to peak drug concentration of approximately 1.5 h and a t1/2 of 2.2 h. One monkey in the oral administration arm of the study had a significant delay in the absorption of the aqueous administered dose. The absolute bioavailability of orally administered beta-L-FddC ranged from 56 to 66%.  (+info)

Metabolic clearance rate is a term used in pharmacology to describe the volume of blood or plasma from which a drug is completely removed per unit time by metabolic processes. It is a measure of the body's ability to eliminate a particular substance and is usually expressed in units of volume (e.g., milliliters or liters) per time (e.g., minutes, hours, or days).

The metabolic clearance rate can be calculated by dividing the total amount of drug eliminated by the plasma concentration of the drug and the time over which it was eliminated. It provides important information about the pharmacokinetics of a drug, including its rate of elimination and the potential for drug-drug interactions that may affect metabolism.

It is worth noting that there are different types of clearance rates, such as renal clearance rate (which refers to the removal of a drug by the kidneys) or hepatic clearance rate (which refers to the removal of a drug by the liver). Metabolic clearance rate specifically refers to the elimination of a drug through metabolic processes, which can occur in various organs throughout the body.

Androstanes are a class of steroidal compounds that have a basic structure consisting of a four-ring core derived from cholesterol. Specifically, androstanes contain a 19-carbon skeleton with a chemical formula of C19H28O or C19H28O2, depending on whether they are alcohols (androgens) or ketones (androstanes), respectively.

The term "androstane" is often used to refer to the parent compound, which has a hydroxyl group (-OH) attached at the C3 position of the steroid nucleus. When this hydroxyl group is replaced by a keto group (-C=O), the resulting compound is called androstane-3,17-dione or simply "androstane."

Androstanes are important precursors in the biosynthesis of various steroid hormones, including testosterone, estrogen, and cortisol. They are also used as intermediates in the synthesis of certain drugs and pharmaceuticals.

17-Ketosteroids are a group of steroid compounds that contain a ketone group at the 17th carbon position in their molecular structure. They are produced as metabolic byproducts of certain hormones, such as androgens and estrogens, in the human body.

The term "17-KS" or "17-ketosteroids" is often used to refer to a class of urinary steroid metabolites that can be measured in the urine to assess adrenal and gonadal function. The measurement of 17-KS is particularly useful in monitoring patients with certain endocrine disorders, such as congenital adrenal hyperplasia or adrenal tumors.

The two major 17-KS that are routinely measured in urine are androsterone and etiocholanolone, which are derived from the metabolism of testosterone and dehydroepiandrosterone (DHEA), respectively. Other 17-KS include tetrahydrocortisone, tetrahydrocortisol, and 5-androstene-3β,17β-diol.

It's worth noting that the measurement of 17-KS has largely been replaced by more specific tests, such as the measurement of individual steroid hormones or their metabolites using mass spectrometry-based methods.

Iodine isotopes are different forms of the chemical element iodine, which have different numbers of neutrons in their nuclei. Iodine has a total of 53 protons in its nucleus, and its stable isotope, iodine-127, has 74 neutrons, giving it a mass number of 127. However, there are also radioactive isotopes of iodine, which have different numbers of neutrons and are therefore unstable.

Radioactive isotopes of iodine emit radiation as they decay towards a stable state. For example, iodine-131 is a commonly used isotope in medical imaging and therapy, with a half-life of about 8 days. It decays by emitting beta particles and gamma rays, making it useful for treating thyroid cancer and other conditions that involve overactive thyroid glands.

Other radioactive iodine isotopes include iodine-123, which has a half-life of about 13 hours and is used in medical imaging, and iodine-125, which has a half-life of about 60 days and is used in brachytherapy (a type of radiation therapy that involves placing radioactive sources directly into or near tumors).

It's important to note that exposure to radioactive iodine isotopes can be harmful, especially if it occurs through inhalation or ingestion. This is because the iodine can accumulate in the thyroid gland and cause damage over time. Therefore, appropriate safety measures must be taken when handling or working with radioactive iodine isotopes.

In the context of pharmacology, "half-life" refers to the time it takes for the concentration or amount of a drug in the body to be reduced by half during its elimination phase. This is typically influenced by factors such as metabolism and excretion rates of the drug. It's a key factor in determining dosage intervals and therapeutic effectiveness of medications, as well as potential side effects or toxicity risks.

Blood glucose, also known as blood sugar, is the concentration of glucose in the blood. Glucose is a simple sugar that serves as the main source of energy for the body's cells. It is carried to each cell through the bloodstream and is absorbed into the cells with the help of insulin, a hormone produced by the pancreas.

The normal range for blood glucose levels in humans is typically between 70 and 130 milligrams per deciliter (mg/dL) when fasting, and less than 180 mg/dL after meals. Levels that are consistently higher than this may indicate diabetes or other metabolic disorders.

Blood glucose levels can be measured through a variety of methods, including fingerstick blood tests, continuous glucose monitoring systems, and laboratory tests. Regular monitoring of blood glucose levels is important for people with diabetes to help manage their condition and prevent complications.

Parenteral infusions refer to the administration of fluids or medications directly into a patient's vein or subcutaneous tissue using a needle or catheter. This route bypasses the gastrointestinal tract and allows for rapid absorption and onset of action. Parenteral infusions can be used to correct fluid and electrolyte imbalances, administer medications that cannot be given orally, provide nutritional support, and deliver blood products. Common types of parenteral infusions include intravenous (IV) drips, IV push, and subcutaneous infusions. It is important that parenteral infusions are administered using aseptic technique to reduce the risk of infection.

Insulin is a hormone produced by the beta cells of the pancreatic islets, primarily in response to elevated levels of glucose in the circulating blood. It plays a crucial role in regulating blood glucose levels and facilitating the uptake and utilization of glucose by peripheral tissues, such as muscle and adipose tissue, for energy production and storage. Insulin also inhibits glucose production in the liver and promotes the storage of excess glucose as glycogen or triglycerides.

Deficiency in insulin secretion or action leads to impaired glucose regulation and can result in conditions such as diabetes mellitus, characterized by chronic hyperglycemia and associated complications. Exogenous insulin is used as a replacement therapy in individuals with diabetes to help manage their blood glucose levels and prevent long-term complications.

The glucose clamp technique is a method used in medical research, particularly in the study of glucose metabolism and insulin action. It's a controlled procedure that aims to maintain a steady state of plasma glucose concentration in an individual for a specific period.

In this technique, a continuous infusion of glucose is administered intravenously at a variable rate to balance the amount of glucose being removed from the circulation (for example, by insulin-stimulated uptake in muscle and fat tissue). This creates a "clamp" of stable plasma glucose concentration.

The rate of glucose infusion is adjusted according to frequent measurements of blood glucose levels, typically every 5 to 10 minutes, to keep the glucose level constant. The glucose clamp technique allows researchers to study how different factors, such as various doses of insulin or other drugs, affect glucose metabolism under standardized conditions.

There are two primary types of glucose clamps: the hyperglycemic clamp and the euglycemic clamp. The former aims to raise and maintain plasma glucose at a higher-than-normal level, while the latter maintains plasma glucose at a normal, euglycemic level.

Intravenous injections are a type of medical procedure where medication or fluids are administered directly into a vein using a needle and syringe. This route of administration is also known as an IV injection. The solution injected enters the patient's bloodstream immediately, allowing for rapid absorption and onset of action. Intravenous injections are commonly used to provide quick relief from symptoms, deliver medications that are not easily absorbed by other routes, or administer fluids and electrolytes in cases of dehydration or severe illness. It is important that intravenous injections are performed using aseptic technique to minimize the risk of infection.

Tritium is not a medical term, but it is a term used in the field of nuclear physics and chemistry. Tritium (symbol: T or 3H) is a radioactive isotope of hydrogen with two neutrons and one proton in its nucleus. It is also known as heavy hydrogen or superheavy hydrogen.

Tritium has a half-life of about 12.3 years, which means that it decays by emitting a low-energy beta particle (an electron) to become helium-3. Due to its radioactive nature and relatively short half-life, tritium is used in various applications, including nuclear weapons, fusion reactors, luminous paints, and medical research.

In the context of medicine, tritium may be used as a radioactive tracer in some scientific studies or medical research, but it is not a term commonly used to describe a medical condition or treatment.

Intravenous (IV) infusion is a medical procedure in which liquids, such as medications, nutrients, or fluids, are delivered directly into a patient's vein through a needle or a catheter. This route of administration allows for rapid absorption and distribution of the infused substance throughout the body. IV infusions can be used for various purposes, including resuscitation, hydration, nutrition support, medication delivery, and blood product transfusion. The rate and volume of the infusion are carefully controlled to ensure patient safety and efficacy of treatment.

Radioimmunoassay (RIA) is a highly sensitive analytical technique used in clinical and research laboratories to measure concentrations of various substances, such as hormones, vitamins, drugs, or tumor markers, in biological samples like blood, urine, or tissues. The method relies on the specific interaction between an antibody and its corresponding antigen, combined with the use of radioisotopes to quantify the amount of bound antigen.

In a typical RIA procedure, a known quantity of a radiolabeled antigen (also called tracer) is added to a sample containing an unknown concentration of the same unlabeled antigen. The mixture is then incubated with a specific antibody that binds to the antigen. During the incubation period, the antibody forms complexes with both the radiolabeled and unlabeled antigens.

After the incubation, the unbound (free) radiolabeled antigen is separated from the antibody-antigen complexes, usually through a precipitation or separation step involving centrifugation, filtration, or chromatography. The amount of radioactivity in the pellet (containing the antibody-antigen complexes) is then measured using a gamma counter or other suitable radiation detection device.

The concentration of the unlabeled antigen in the sample can be determined by comparing the ratio of bound to free radiolabeled antigen in the sample to a standard curve generated from known concentrations of unlabeled antigen and their corresponding bound/free ratios. The higher the concentration of unlabeled antigen in the sample, the lower the amount of radiolabeled antigen that will bind to the antibody, resulting in a lower bound/free ratio.

Radioimmunoassays offer high sensitivity, specificity, and accuracy, making them valuable tools for detecting and quantifying low levels of various substances in biological samples. However, due to concerns about radiation safety and waste disposal, alternative non-isotopic immunoassay techniques like enzyme-linked immunosorbent assays (ELISAs) have become more popular in recent years.

In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."

1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.

2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.

3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.

4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).

Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.

Testosterone is a steroid hormone that belongs to androsten class of hormones. It is primarily secreted by the Leydig cells in the testes of males and, to a lesser extent, by the ovaries and adrenal glands in females. Testosterone is the main male sex hormone and anabolic steroid. It plays a key role in the development of masculine characteristics, such as body hair and muscle mass, and contributes to bone density, fat distribution, red cell production, and sex drive. In females, testosterone contributes to sexual desire and bone health. Testosterone is synthesized from cholesterol and its production is regulated by luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Glucose is a simple monosaccharide (or single sugar) that serves as the primary source of energy for living organisms. It's a fundamental molecule in biology, often referred to as "dextrose" or "grape sugar." Glucose has the molecular formula C6H12O6 and is vital to the functioning of cells, especially those in the brain and nervous system.

In the body, glucose is derived from the digestion of carbohydrates in food, and it's transported around the body via the bloodstream to cells where it can be used for energy. Cells convert glucose into a usable form through a process called cellular respiration, which involves a series of metabolic reactions that generate adenosine triphosphate (ATP)—the main currency of energy in cells.

Glucose is also stored in the liver and muscles as glycogen, a polysaccharide (multiple sugar) that can be broken down back into glucose when needed for energy between meals or during physical activity. Maintaining appropriate blood glucose levels is crucial for overall health, and imbalances can lead to conditions such as diabetes mellitus.

The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:

1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.

Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.

I believe there might be a misunderstanding in your question. "Dogs" is not a medical term or condition. It is the common name for a domesticated carnivore of the family Canidae, specifically the genus Canis, which includes wolves, foxes, and other extant and extinct species of mammals. Dogs are often kept as pets and companions, and they have been bred in a wide variety of forms and sizes for different purposes, such as hunting, herding, guarding, assisting police and military forces, and providing companionship and emotional support.

If you meant to ask about a specific medical condition or term related to dogs, please provide more context so I can give you an accurate answer.

Glucagon is a hormone produced by the alpha cells of the pancreas. Its main function is to regulate glucose levels in the blood by stimulating the liver to convert stored glycogen into glucose, which can then be released into the bloodstream. This process helps to raise blood sugar levels when they are too low, such as during hypoglycemia.

Glucagon is a 29-amino acid polypeptide that is derived from the preproglucagon protein. It works by binding to glucagon receptors on liver cells, which triggers a series of intracellular signaling events that lead to the activation of enzymes involved in glycogen breakdown.

In addition to its role in glucose regulation, glucagon has also been shown to have other physiological effects, such as promoting lipolysis (the breakdown of fat) and inhibiting gastric acid secretion. Glucagon is often used clinically in the treatment of hypoglycemia, as well as in diagnostic tests to assess pancreatic function.

Carbon isotopes are variants of the chemical element carbon that have different numbers of neutrons in their atomic nuclei. The most common and stable isotope of carbon is carbon-12 (^{12}C), which contains six protons and six neutrons. However, carbon can also come in other forms, known as isotopes, which contain different numbers of neutrons.

Carbon-13 (^{13}C) is a stable isotope of carbon that contains seven neutrons in its nucleus. It makes up about 1.1% of all carbon found on Earth and is used in various scientific applications, such as in tracing the metabolic pathways of organisms or in studying the age of fossilized materials.

Carbon-14 (^{14}C), also known as radiocarbon, is a radioactive isotope of carbon that contains eight neutrons in its nucleus. It is produced naturally in the atmosphere through the interaction of cosmic rays with nitrogen gas. Carbon-14 has a half-life of about 5,730 years, which makes it useful for dating organic materials, such as archaeological artifacts or fossils, up to around 60,000 years old.

Carbon isotopes are important in many scientific fields, including geology, biology, and medicine, and are used in a variety of applications, from studying the Earth's climate history to diagnosing medical conditions.

Growth Hormone (GH), also known as somatotropin, is a peptide hormone secreted by the somatotroph cells in the anterior pituitary gland. It plays a crucial role in regulating growth, cell reproduction, and regeneration by stimulating the production of another hormone called insulin-like growth factor 1 (IGF-1) in the liver and other tissues. GH also has important metabolic functions, such as increasing glucose levels, enhancing protein synthesis, and reducing fat storage. Its secretion is regulated by two hypothalamic hormones: growth hormone-releasing hormone (GHRH), which stimulates its release, and somatostatin (SRIF), which inhibits its release. Abnormal levels of GH can lead to various medical conditions, such as dwarfism or gigantism if there are deficiencies or excesses, respectively.

Insulin resistance is a condition in which the body's cells become less responsive to insulin, a hormone produced by the pancreas that regulates blood sugar levels. In response to this decreased sensitivity, the pancreas produces more insulin to help glucose enter the cells. However, over time, the pancreas may not be able to keep up with the increased demand for insulin, leading to high levels of glucose in the blood and potentially resulting in type 2 diabetes, prediabetes, or other health issues such as metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease. Insulin resistance is often associated with obesity, physical inactivity, and genetic factors.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Pregnancy is a physiological state or condition where a fertilized egg (zygote) successfully implants and grows in the uterus of a woman, leading to the development of an embryo and finally a fetus. This process typically spans approximately 40 weeks, divided into three trimesters, and culminates in childbirth. Throughout this period, numerous hormonal and physical changes occur to support the growing offspring, including uterine enlargement, breast development, and various maternal adaptations to ensure the fetus's optimal growth and well-being.

Microsomes, liver refers to a subcellular fraction of liver cells (hepatocytes) that are obtained during tissue homogenization and subsequent centrifugation. These microsomal fractions are rich in membranous structures known as the endoplasmic reticulum (ER), particularly the rough ER. They are involved in various important cellular processes, most notably the metabolism of xenobiotics (foreign substances) including drugs, toxins, and carcinogens.

The liver microsomes contain a variety of enzymes, such as cytochrome P450 monooxygenases, that are crucial for phase I drug metabolism. These enzymes help in the oxidation, reduction, or hydrolysis of xenobiotics, making them more water-soluble and facilitating their excretion from the body. Additionally, liver microsomes also host other enzymes involved in phase II conjugation reactions, where the metabolites from phase I are further modified by adding polar molecules like glucuronic acid, sulfate, or acetyl groups.

In summary, liver microsomes are a subcellular fraction of liver cells that play a significant role in the metabolism and detoxification of xenobiotics, contributing to the overall protection and maintenance of cellular homeostasis within the body.

Mucociliary clearance is a vital defense mechanism of the respiratory system that involves the coordinated movement of tiny hair-like structures called cilia, which are present on the surface of the respiratory epithelium, and the mucus layer. This mechanism helps to trap inhaled particles, microorganisms, and other harmful substances and move them away from the lungs towards the upper airways, where they can be swallowed or coughed out.

The cilia beat in a coordinated manner, moving in a wave-like motion to propel the mucus layer upwards. This continuous movement helps to clear the airways of any debris and maintain a clean and healthy respiratory system. Mucociliary clearance plays an essential role in preventing respiratory infections and maintaining lung function. Any impairment in this mechanism, such as due to smoking or certain respiratory conditions, can increase the risk of respiratory infections and other related health issues.

Pharmaceutical preparations refer to the various forms of medicines that are produced by pharmaceutical companies, which are intended for therapeutic or prophylactic use. These preparations consist of an active ingredient (the drug) combined with excipients (inactive ingredients) in a specific formulation and dosage form.

The active ingredient is the substance that has a therapeutic effect on the body, while the excipients are added to improve the stability, palatability, bioavailability, or administration of the drug. Examples of pharmaceutical preparations include tablets, capsules, solutions, suspensions, emulsions, ointments, creams, and injections.

The production of pharmaceutical preparations involves a series of steps that ensure the quality, safety, and efficacy of the final product. These steps include the selection and testing of raw materials, formulation development, manufacturing, packaging, labeling, and storage. Each step is governed by strict regulations and guidelines to ensure that the final product meets the required standards for use in medical practice.

A kidney, in medical terms, is one of two bean-shaped organs located in the lower back region of the body. They are essential for maintaining homeostasis within the body by performing several crucial functions such as:

1. Regulation of water and electrolyte balance: Kidneys help regulate the amount of water and various electrolytes like sodium, potassium, and calcium in the bloodstream to maintain a stable internal environment.

2. Excretion of waste products: They filter waste products from the blood, including urea (a byproduct of protein metabolism), creatinine (a breakdown product of muscle tissue), and other harmful substances that result from normal cellular functions or external sources like medications and toxins.

3. Endocrine function: Kidneys produce several hormones with important roles in the body, such as erythropoietin (stimulates red blood cell production), renin (regulates blood pressure), and calcitriol (activated form of vitamin D that helps regulate calcium homeostasis).

4. pH balance regulation: Kidneys maintain the proper acid-base balance in the body by excreting either hydrogen ions or bicarbonate ions, depending on whether the blood is too acidic or too alkaline.

5. Blood pressure control: The kidneys play a significant role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS), which constricts blood vessels and promotes sodium and water retention to increase blood volume and, consequently, blood pressure.

Anatomically, each kidney is approximately 10-12 cm long, 5-7 cm wide, and 3 cm thick, with a weight of about 120-170 grams. They are surrounded by a protective layer of fat and connected to the urinary system through the renal pelvis, ureters, bladder, and urethra.

Glucuronides are conjugated compounds formed in the liver by the attachment of glucuronic acid to a variety of molecules, including drugs, hormones, and environmental toxins. This process, known as glucuronidation, is catalyzed by enzymes called UDP-glucuronosyltransferases (UGTs) and increases the water solubility of these compounds, allowing them to be more easily excreted from the body through urine or bile.

Glucuronidation plays a crucial role in the detoxification and elimination of many substances, including drugs and toxins. However, in some cases, glucuronides can also be hydrolyzed back into their original forms by enzymes called β-glucuronidases, which can lead to reabsorption of the parent compound and prolong its effects or toxicity.

Overall, understanding the metabolism and disposition of glucuronides is important for predicting drug interactions, pharmacokinetics, and potential adverse effects.

Hepatocytes are the predominant type of cells in the liver, accounting for about 80% of its cytoplasmic mass. They play a key role in protein synthesis, protein storage, transformation of carbohydrates, synthesis of cholesterol, bile salts and phospholipids, detoxification, modification, and excretion of exogenous and endogenous substances, initiation of formation and secretion of bile, and enzyme production. Hepatocytes are essential for the maintenance of homeostasis in the body.

Aldehyde oxidase is an enzyme found in the liver and other organs that helps to metabolize (break down) various substances, including drugs, alcohol, and environmental toxins. It does this by catalyzing the oxidation of aldehydes, which are organic compounds containing a functional group consisting of a carbon atom bonded to a hydrogen atom and a double bond to an oxygen atom. Aldehyde oxidase is a member of the molybdenum-containing oxidoreductase family, which also includes xanthine oxidase and sulfite oxidase. These enzymes all contain a molybdenum cofactor that plays a critical role in their catalytic activity.

Aldehyde oxidase is an important enzyme in the metabolism of many drugs, as it can convert them into more water-soluble compounds that can be easily excreted from the body. However, variations in the activity of this enzyme between individuals can lead to differences in drug metabolism and response. Some people may have higher or lower levels of aldehyde oxidase activity, which can affect how quickly they metabolize certain drugs and whether they experience adverse effects.

In addition to its role in drug metabolism, aldehyde oxidase has been implicated in the development of various diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. For example, elevated levels of aldehydes produced by lipid peroxidation have been linked to oxidative stress and inflammation, which can contribute to the progression of these conditions. Aldehyde oxidase may also play a role in the detoxification of environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs), which have been associated with an increased risk of cancer.

Overall, aldehyde oxidase is an important enzyme that plays a critical role in the metabolism of drugs and other substances, as well as in the development of various diseases. Understanding its activity and regulation may help to develop new strategies for treating or preventing these conditions.

Technetium Tc 99m Pentetate is a radioactive pharmaceutical preparation used as a radiopharmaceutical agent in medical imaging. It is a salt of technetium-99m, a metastable nuclear isomer of technetium-99, which emits gamma rays and has a half-life of 6 hours.

Technetium Tc 99m Pentetate is used in various diagnostic procedures, including renal imaging, brain scans, lung perfusion studies, and bone scans. It is distributed throughout the body after intravenous injection and is excreted primarily by the kidneys, making it useful for evaluating renal function and detecting abnormalities in the urinary tract.

The compound itself is a colorless, sterile, pyrogen-free solution that is typically supplied in a lead shielded container to protect against radiation exposure. It should be used promptly after preparation and handled with care to minimize radiation exposure to healthcare workers and patients.

The Cytochrome P-450 (CYP450) enzyme system is a group of enzymes found primarily in the liver, but also in other organs such as the intestines, lungs, and skin. These enzymes play a crucial role in the metabolism and biotransformation of various substances, including drugs, environmental toxins, and endogenous compounds like hormones and fatty acids.

The name "Cytochrome P-450" refers to the unique property of these enzymes to bind to carbon monoxide (CO) and form a complex that absorbs light at a wavelength of 450 nm, which can be detected spectrophotometrically.

The CYP450 enzyme system is involved in Phase I metabolism of xenobiotics, where it catalyzes oxidation reactions such as hydroxylation, dealkylation, and epoxidation. These reactions introduce functional groups into the substrate molecule, which can then undergo further modifications by other enzymes during Phase II metabolism.

There are several families and subfamilies of CYP450 enzymes, each with distinct substrate specificities and functions. Some of the most important CYP450 enzymes include:

1. CYP3A4: This is the most abundant CYP450 enzyme in the human liver and is involved in the metabolism of approximately 50% of all drugs. It also metabolizes various endogenous compounds like steroids, bile acids, and vitamin D.
2. CYP2D6: This enzyme is responsible for the metabolism of many psychotropic drugs, including antidepressants, antipsychotics, and beta-blockers. It also metabolizes some endogenous compounds like dopamine and serotonin.
3. CYP2C9: This enzyme plays a significant role in the metabolism of warfarin, phenytoin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
4. CYP2C19: This enzyme is involved in the metabolism of proton pump inhibitors, antidepressants, and clopidogrel.
5. CYP2E1: This enzyme metabolizes various xenobiotics like alcohol, acetaminophen, and carbon tetrachloride, as well as some endogenous compounds like fatty acids and prostaglandins.

Genetic polymorphisms in CYP450 enzymes can significantly affect drug metabolism and response, leading to interindividual variability in drug efficacy and toxicity. Understanding the role of CYP450 enzymes in drug metabolism is crucial for optimizing pharmacotherapy and minimizing adverse effects.

Glucuronates are not a medical term per se, but they refer to salts or esters of glucuronic acid, a organic compound that is a derivative of glucose. In the context of medical and biological sciences, glucuronidation is a common detoxification process in which glucuronic acid is conjugated to a wide variety of molecules, including drugs, hormones, and environmental toxins, to make them more water-soluble and facilitate their excretion from the body through urine or bile.

The process of glucuronidation is catalyzed by enzymes called UDP-glucuronosyltransferases (UGTs), which are found in various tissues, including the liver, intestines, and kidneys. The resulting glucuronides can be excreted directly or further metabolized before excretion.

Therefore, "glucuronates" can refer to the chemical compounds that result from this process of conjugation with glucuronic acid, as well as the therapeutic potential of enhancing or inhibiting glucuronidation for various clinical applications.

Dealkylation is a chemical process that involves the removal of an alkyl group from a molecule. In the context of medical and biological sciences, dealkylation often refers to the breakdown of drugs or other xenobiotics (foreign substances) in the body by enzymes.

Dealkylation is one of the major metabolic pathways for the biotransformation of many drugs, including chemotherapeutic agents, opioids, and benzodiazepines. This process can result in the formation of more polar and water-soluble metabolites, which can then be excreted from the body through the urine or bile.

Dealkylation can occur via several mechanisms, including oxidative dealkylation catalyzed by cytochrome P450 enzymes, as well as non-oxidative dealkylation mediated by other enzymes. The specific dealkylation pathway depends on the structure of the substrate and the type of enzyme involved.

Cytochrome P-450 CYP3A is a subfamily of the cytochrome P-450 enzyme superfamily, which are primarily involved in drug metabolism in the human body. These enzymes are found predominantly in the liver, but also in other tissues such as the small intestine, kidneys, and brain.

CYP3A enzymes are responsible for metabolizing a wide variety of drugs, including many statins, benzodiazepines, antidepressants, and opioids. They can also metabolize endogenous compounds such as steroids and bile acids. The activity of CYP3A enzymes can be influenced by various factors, including genetic polymorphisms, age, sex, pregnancy, and the presence of other drugs or diseases.

The name "cytochrome P-450" refers to the fact that these enzymes contain a heme group that absorbs light at a wavelength of 450 nanometers when it is complexed with carbon monoxide. The term "CYP3A" denotes the specific subfamily of cytochrome P-450 enzymes that share a high degree of sequence similarity and function.

Antipyrine is a chemical compound that was commonly used as a fever reducer and pain reliever in the past. It is a type of phenylpyrazole antipyretic and analgesic. However, due to its potential for causing liver damage and other side effects, it has largely been replaced by other medications and is not widely used in modern medicine.

The medical definition of Antipyrine refers to this specific chemical compound with the formula C11H13N3O2, and not to any broader category of drugs or substances. It is a white crystalline powder that is soluble in alcohol, chloroform, and ether, but insoluble in water.

Antipyrine was first synthesized in 1883 and was widely used as a fever reducer and pain reliever until the mid-20th century. However, its use declined due to concerns about its safety profile, including the potential for liver damage, skin reactions, and other side effects.

Today, Antipyrine is still used in some medical applications, such as in the measurement of earwax conductivity as a way to assess hearing function. It may also be used in some topical creams and ointments for pain relief. However, its use as a systemic medication is generally not recommended due to its potential for causing harm.

Biotransformation is the metabolic modification of a chemical compound, typically a xenobiotic (a foreign chemical substance found within an living organism), by a biological system. This process often involves enzymatic conversion of the parent compound to one or more metabolites, which may be more or less active, toxic, or mutagenic than the original substance.

In the context of pharmacology and toxicology, biotransformation is an important aspect of drug metabolism and elimination from the body. The liver is the primary site of biotransformation, but other organs such as the kidneys, lungs, and gastrointestinal tract can also play a role.

Biotransformation can occur in two phases: phase I reactions involve functionalization of the parent compound through oxidation, reduction, or hydrolysis, while phase II reactions involve conjugation of the metabolite with endogenous molecules such as glucuronic acid, sulfate, or acetate to increase its water solubility and facilitate excretion.

A drug interaction is the effect of combining two or more drugs, or a drug and another substance (such as food or alcohol), which can alter the effectiveness or side effects of one or both of the substances. These interactions can be categorized as follows:

1. Pharmacodynamic interactions: These occur when two or more drugs act on the same target organ or receptor, leading to an additive, synergistic, or antagonistic effect. For example, taking a sedative and an antihistamine together can result in increased drowsiness due to their combined depressant effects on the central nervous system.
2. Pharmacokinetic interactions: These occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug. For example, taking certain antibiotics with grapefruit juice can increase the concentration of the antibiotic in the bloodstream, leading to potential toxicity.
3. Food-drug interactions: Some drugs may interact with specific foods, affecting their absorption, metabolism, or excretion. An example is the interaction between warfarin (a blood thinner) and green leafy vegetables, which can increase the risk of bleeding due to enhanced vitamin K absorption from the vegetables.
4. Drug-herb interactions: Some herbal supplements may interact with medications, leading to altered drug levels or increased side effects. For instance, St. John's Wort can decrease the effectiveness of certain antidepressants and oral contraceptives by inducing their metabolism.
5. Drug-alcohol interactions: Alcohol can interact with various medications, causing additive sedative effects, impaired judgment, or increased risk of liver damage. For example, combining alcohol with benzodiazepines or opioids can lead to dangerous levels of sedation and respiratory depression.

It is essential for healthcare providers and patients to be aware of potential drug interactions to minimize adverse effects and optimize treatment outcomes.

The term "Area Under Curve" (AUC) is commonly used in the medical field, particularly in the analysis of diagnostic tests or pharmacokinetic studies. The AUC refers to the mathematical calculation of the area between a curve and the x-axis in a graph, typically representing a concentration-time profile.

In the context of diagnostic tests, the AUC is used to evaluate the performance of a test by measuring the entire two-dimensional area underneath the receiver operating characteristic (ROC) curve, which plots the true positive rate (sensitivity) against the false positive rate (1-specificity) at various threshold settings. The AUC ranges from 0 to 1, where a higher AUC indicates better test performance:

* An AUC of 0.5 suggests that the test is no better than chance.
* An AUC between 0.7 and 0.8 implies moderate accuracy.
* An AUC between 0.8 and 0.9 indicates high accuracy.
* An AUC greater than 0.9 signifies very high accuracy.

In pharmacokinetic studies, the AUC is used to assess drug exposure over time by calculating the area under a plasma concentration-time curve (AUC(0-t) or AUC(0-\∞)) following drug administration. This value can help determine dosing regimens and evaluate potential drug interactions:

* AUC(0-t): Represents the area under the plasma concentration-time curve from time zero to the last measurable concentration (t).
* AUC(0-\∞): Refers to the area under the plasma concentration-time curve from time zero to infinity, which estimates total drug exposure.

Tissue distribution, in the context of pharmacology and toxicology, refers to the way that a drug or xenobiotic (a chemical substance found within an organism that is not naturally produced by or expected to be present within that organism) is distributed throughout the body's tissues after administration. It describes how much of the drug or xenobiotic can be found in various tissues and organs, and is influenced by factors such as blood flow, lipid solubility, protein binding, and the permeability of cell membranes. Understanding tissue distribution is important for predicting the potential effects of a drug or toxin on different parts of the body, and for designing drugs with improved safety and efficacy profiles.

Pharmacokinetics is the branch of pharmacology that deals with the movement of a drug in the body after administration. It involves the processes of absorption, distribution, metabolism, and excretion (ADME) of drugs.

1. Absorption: This is the process by which a drug is taken into the body and made available for distribution to the site of action.
2. Distribution: This refers to the dispersion of the drug throughout the body after absorption. It involves the transfer of the drug from the bloodstream into various tissues and organs.
3. Metabolism: This is the biotransformation of a drug by enzymes, usually in the liver, into metabolic products (also known as metabolites). These metabolites may be pharmacologically active, inactive, or toxic.
4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, typically through the kidneys (urine), lungs (exhaled air), skin (sweat), or gastrointestinal tract (feces).

Understanding pharmacokinetics is crucial for determining the optimal dosage regimen of a drug to achieve and maintain its therapeutic concentration in the body while minimizing potential side effects.

Thyroxine (T4) is a type of hormone produced and released by the thyroid gland, a small butterfly-shaped endocrine gland located in the front of your neck. It is one of two major hormones produced by the thyroid gland, with the other being triiodothyronine (T3).

Thyroxine plays a crucial role in regulating various metabolic processes in the body, including growth, development, and energy expenditure. Specifically, T4 helps to control the rate at which your body burns calories for energy, regulates protein, fat, and carbohydrate metabolism, and influences the body's sensitivity to other hormones.

T4 is produced by combining iodine and tyrosine, an amino acid found in many foods. Once produced, T4 circulates in the bloodstream and gets converted into its active form, T3, in various tissues throughout the body. Thyroxine has a longer half-life than T3, which means it remains active in the body for a more extended period.

Abnormal levels of thyroxine can lead to various medical conditions, such as hypothyroidism (underactive thyroid) or hyperthyroidism (overactive thyroid). These conditions can cause a range of symptoms, including weight gain or loss, fatigue, mood changes, and changes in heart rate and blood pressure.

Oral administration is a route of giving medications or other substances by mouth. This can be in the form of tablets, capsules, liquids, pastes, or other forms that can be swallowed. Once ingested, the substance is absorbed through the gastrointestinal tract and enters the bloodstream to reach its intended target site in the body. Oral administration is a common and convenient route of medication delivery, but it may not be appropriate for all substances or in certain situations, such as when rapid onset of action is required or when the patient has difficulty swallowing.

The Mononuclear Phagocyte System (MPS) is a network of specialized immune cells distributed throughout the body, primarily consisting of monocytes, macrophages, and dendritic cells. These cells share a common bone marrow-derived precursor and play crucial roles in innate and adaptive immunity. They are involved in various functions such as:

1. Phagocytosis: engulfing and destroying foreign particles, microbes, and cellular debris.
2. Antigen presentation: processing and presenting antigens to T-cells to initiate an adaptive immune response.
3. Cytokine production: releasing pro- and anti-inflammatory cytokines to regulate immune responses and maintain tissue homeostasis.
4. Immune regulation: modulating the activity of other immune cells, including T-cells, B-cells, and natural killer (NK) cells.

The MPS is essential for maintaining tissue integrity, fighting infections, and orchestrating immune responses. Its components are found in various tissues, including the liver (Kupffer cells), spleen, lymph nodes, bone marrow, and connective tissues.

C-peptide is a byproduct that is produced when the hormone insulin is generated in the body. Insulin is a hormone that helps regulate blood sugar levels, and it is produced in the pancreas by specialized cells called beta cells. When these cells produce insulin, they also generate C-peptide as a part of the same process.

C-peptide is often used as a marker to measure the body's insulin production. By measuring C-peptide levels in the blood, healthcare providers can get an idea of how much insulin the body is producing on its own. This can be helpful in diagnosing and monitoring conditions such as diabetes, which is characterized by impaired insulin production or function.

It's worth noting that C-peptide is not typically used as a treatment for any medical conditions. Instead, it is primarily used as a diagnostic tool to help healthcare providers better understand their patients' health status and make informed treatment decisions.

Midazolam is a medication from the class of drugs known as benzodiazepines. It works by enhancing the effect of a neurotransmitter called gamma-aminobutyric acid (GABA), which has a calming effect on the brain and nervous system. Midazolam is often used for its sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant properties.

Medically, midazolam is used for various purposes, including:

1. Preoperative medication (sedation before surgery)
2. Procedural sedation (for minor surgical or diagnostic procedures)
3. Treatment of seizures (status epilepticus)
4. Sedation in critically ill patients
5. As an adjunct to anesthesia during surgeries
6. Treatment of alcohol withdrawal symptoms
7. To induce amnesia for certain medical or dental procedures

Midazolam is available in various forms, such as tablets, intravenous (IV) solutions, and intranasal sprays. It has a rapid onset of action and a short duration, making it suitable for brief, intermittent procedures. However, midazolam can cause side effects like drowsiness, confusion, respiratory depression, and memory impairment. Therefore, its use should be carefully monitored by healthcare professionals.

Nonesterified fatty acids (NEFA), also known as free fatty acids (FFA), refer to fatty acid molecules that are not bound to glycerol in the form of triglycerides or other esters. In the bloodstream, NEFAs are transported while bound to albumin and can serve as a source of energy for peripheral tissues. Under normal physiological conditions, NEFA levels are tightly regulated by the body; however, elevated NEFA levels have been associated with various metabolic disorders such as insulin resistance, obesity, and type 2 diabetes.

Biological availability is a term used in pharmacology and toxicology that refers to the degree and rate at which a drug or other substance is absorbed into the bloodstream and becomes available at the site of action in the body. It is a measure of the amount of the substance that reaches the systemic circulation unchanged, after administration by any route (such as oral, intravenous, etc.).

The biological availability (F) of a drug can be calculated using the area under the curve (AUC) of the plasma concentration-time profile after extravascular and intravenous dosing, according to the following formula:

F = (AUCex/AUCiv) x (Doseiv/Doseex)

where AUCex is the AUC after extravascular dosing, AUCiv is the AUC after intravenous dosing, Doseiv is the intravenous dose, and Doseex is the extravascular dose.

Biological availability is an important consideration in drug development and therapy, as it can affect the drug's efficacy, safety, and dosage regimen. Drugs with low biological availability may require higher doses to achieve the desired therapeutic effect, while drugs with high biological availability may have a more rapid onset of action and require lower doses to avoid toxicity.

Biological models, also known as physiological models or organismal models, are simplified representations of biological systems, processes, or mechanisms that are used to understand and explain the underlying principles and relationships. These models can be theoretical (conceptual or mathematical) or physical (such as anatomical models, cell cultures, or animal models). They are widely used in biomedical research to study various phenomena, including disease pathophysiology, drug action, and therapeutic interventions.

Examples of biological models include:

1. Mathematical models: These use mathematical equations and formulas to describe complex biological systems or processes, such as population dynamics, metabolic pathways, or gene regulation networks. They can help predict the behavior of these systems under different conditions and test hypotheses about their underlying mechanisms.
2. Cell cultures: These are collections of cells grown in a controlled environment, typically in a laboratory dish or flask. They can be used to study cellular processes, such as signal transduction, gene expression, or metabolism, and to test the effects of drugs or other treatments on these processes.
3. Animal models: These are living organisms, usually vertebrates like mice, rats, or non-human primates, that are used to study various aspects of human biology and disease. They can provide valuable insights into the pathophysiology of diseases, the mechanisms of drug action, and the safety and efficacy of new therapies.
4. Anatomical models: These are physical representations of biological structures or systems, such as plastic models of organs or tissues, that can be used for educational purposes or to plan surgical procedures. They can also serve as a basis for developing more sophisticated models, such as computer simulations or 3D-printed replicas.

Overall, biological models play a crucial role in advancing our understanding of biology and medicine, helping to identify new targets for therapeutic intervention, develop novel drugs and treatments, and improve human health.

Sprague-Dawley rats are a strain of albino laboratory rats that are widely used in scientific research. They were first developed by researchers H.H. Sprague and R.C. Dawley in the early 20th century, and have since become one of the most commonly used rat strains in biomedical research due to their relatively large size, ease of handling, and consistent genetic background.

Sprague-Dawley rats are outbred, which means that they are genetically diverse and do not suffer from the same limitations as inbred strains, which can have reduced fertility and increased susceptibility to certain diseases. They are also characterized by their docile nature and low levels of aggression, making them easier to handle and study than some other rat strains.

These rats are used in a wide variety of research areas, including toxicology, pharmacology, nutrition, cancer, and behavioral studies. Because they are genetically diverse, Sprague-Dawley rats can be used to model a range of human diseases and conditions, making them an important tool in the development of new drugs and therapies.

High-performance liquid chromatography (HPLC) is a type of chromatography that separates and analyzes compounds based on their interactions with a stationary phase and a mobile phase under high pressure. The mobile phase, which can be a gas or liquid, carries the sample mixture through a column containing the stationary phase.

In HPLC, the mobile phase is a liquid, and it is pumped through the column at high pressures (up to several hundred atmospheres) to achieve faster separation times and better resolution than other types of liquid chromatography. The stationary phase can be a solid or a liquid supported on a solid, and it interacts differently with each component in the sample mixture, causing them to separate as they travel through the column.

HPLC is widely used in analytical chemistry, pharmaceuticals, biotechnology, and other fields to separate, identify, and quantify compounds present in complex mixtures. It can be used to analyze a wide range of substances, including drugs, hormones, vitamins, pigments, flavors, and pollutants. HPLC is also used in the preparation of pure samples for further study or use.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

"Inbred strains of rats" are genetically identical rodents that have been produced through many generations of brother-sister mating. This results in a high degree of homozygosity, where the genes at any particular locus in the genome are identical in all members of the strain.

Inbred strains of rats are widely used in biomedical research because they provide a consistent and reproducible genetic background for studying various biological phenomena, including the effects of drugs, environmental factors, and genetic mutations on health and disease. Additionally, inbred strains can be used to create genetically modified models of human diseases by introducing specific mutations into their genomes.

Some commonly used inbred strains of rats include the Wistar Kyoto (WKY), Sprague-Dawley (SD), and Fischer 344 (F344) rat strains. Each strain has its own unique genetic characteristics, making them suitable for different types of research.

Iodine radioisotopes are radioactive isotopes of the element iodine, which decays and emits radiation in the form of gamma rays. Some commonly used iodine radioisotopes include I-123, I-125, I-131. These radioisotopes have various medical applications such as in diagnostic imaging, therapy for thyroid disorders, and cancer treatment.

For example, I-131 is commonly used to treat hyperthyroidism and differentiated thyroid cancer due to its ability to destroy thyroid tissue. On the other hand, I-123 is often used in nuclear medicine scans of the thyroid gland because it emits gamma rays that can be detected by a gamma camera, allowing for detailed images of the gland's structure and function.

It is important to note that handling and administering radioisotopes require specialized training and safety precautions due to their radiation-emitting properties.

Glucuronosyltransferase (UDP-glucuronosyltransferase) is an enzyme belonging to the family of glycosyltransferases. It plays a crucial role in the process of biotransformation and detoxification of various endogenous and exogenous substances, including drugs, hormones, and environmental toxins, in the liver and other organs.

The enzyme functions by transferring a glucuronic acid moiety from a donor molecule, uridine diphosphate glucuronic acid (UDP-GlcUA), to an acceptor molecule, which can be a variety of hydrophobic compounds. This reaction results in the formation of a more water-soluble glucuronide conjugate, facilitating the excretion of the substrate through urine or bile.

There are multiple isoforms of glucuronosyltransferase, classified into two main families: UGT1 and UGT2. These isoforms exhibit different substrate specificities and tissue distributions, allowing for a wide range of compounds to be metabolized through the glucuronidation pathway.

In summary, Glucuronosyltransferase is an essential enzyme in the detoxification process, facilitating the elimination of various substances from the body by conjugating them with a glucuronic acid moiety.

Hormones are defined as chemical messengers that are produced by endocrine glands or specialized cells and are transported through the bloodstream to tissues and organs, where they elicit specific responses. They play crucial roles in regulating various physiological processes such as growth, development, metabolism, reproduction, and mood. Examples of hormones include insulin, estrogen, testosterone, adrenaline, and thyroxine.

Hydrocortisone is a synthetic glucocorticoid, which is a class of steroid hormones. It is identical to the naturally occurring cortisol, a hormone produced by the adrenal gland that helps regulate metabolism and helps your body respond to stress. Hydrocortisone has anti-inflammatory effects and is used to treat various inflammatory conditions such as allergies, skin disorders, and autoimmune diseases. It works by suppressing the immune system's response to reduce swelling, redness, itching, and other symptoms caused by inflammation.

Hydrocortisone is available in different forms, including oral tablets, topical creams, lotions, gels, and ointments, as well as injectable solutions. The specific use and dosage depend on the condition being treated and the individual patient's medical history and current health status.

As with any medication, hydrocortisone can have side effects, especially when used in high doses or for extended periods. Common side effects include increased appetite, weight gain, mood changes, insomnia, and skin thinning. Long-term use of hydrocortisone may also increase the risk of developing osteoporosis, diabetes, cataracts, and other health problems. Therefore, it is essential to follow your healthcare provider's instructions carefully when using this medication.

Hydroxylation is a biochemical process that involves the addition of a hydroxyl group (-OH) to a molecule, typically a steroid or xenobiotic compound. This process is primarily catalyzed by enzymes called hydroxylases, which are found in various tissues throughout the body.

In the context of medicine and biochemistry, hydroxylation can have several important functions:

1. Drug metabolism: Hydroxylation is a common way that the liver metabolizes drugs and other xenobiotic compounds. By adding a hydroxyl group to a drug molecule, it becomes more polar and water-soluble, which facilitates its excretion from the body.
2. Steroid hormone biosynthesis: Hydroxylation is an essential step in the biosynthesis of many steroid hormones, including cortisol, aldosterone, and the sex hormones estrogen and testosterone. These hormones are synthesized from cholesterol through a series of enzymatic reactions that involve hydroxylation at various steps.
3. Vitamin D activation: Hydroxylation is also necessary for the activation of vitamin D in the body. In order to become biologically active, vitamin D must undergo two successive hydroxylations, first in the liver and then in the kidneys.
4. Toxin degradation: Some toxic compounds can be rendered less harmful through hydroxylation. For example, phenol, a toxic compound found in cigarette smoke and some industrial chemicals, can be converted to a less toxic form through hydroxylation by enzymes in the liver.

Overall, hydroxylation is an important biochemical process that plays a critical role in various physiological functions, including drug metabolism, hormone biosynthesis, and toxin degradation.

Cytochrome P-450 CYP2D6 is a specific isoenzyme belonging to the Cytochrome P-450 (CYP) family of enzymes, which are primarily located in the liver and play a crucial role in the metabolism of various drugs and xenobiotics. The term "P-450" refers to the absorption spectrum of these enzymes when they are combined with carbon monoxide, exhibiting a peak absorbance at 450 nanometers.

CYP2D6 is involved in the metabolism of approximately 20-25% of clinically prescribed drugs, including many antidepressants, neuroleptics, beta-blockers, opioids, and antiarrhythmics. This enzyme can demonstrate genetic polymorphisms, leading to variations in drug metabolism rates among individuals. These genetic differences can result in four distinct phenotypes: poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM), and ultra-rapid metabolizers (UM).

Poor metabolizers have decreased or absent CYP2D6 enzyme activity due to genetic mutations, leading to an accumulation of drugs in the body and increased susceptibility to adverse drug reactions. In contrast, ultra-rapid metabolizers possess multiple copies of the functional CYP2D6 gene, resulting in enhanced enzymatic activity and rapid drug clearance. This can lead to therapeutic failure due to insufficient drug exposure at the target site.

Understanding the genetic variations in CYP2D6 is essential for personalized medicine, as it allows healthcare providers to tailor drug therapy based on an individual's metabolic capacity and minimize the risk of adverse reactions or treatment failures.

Its metabolic clearance rate is 80 L/day/m2. Ovarian tumors have been found to express steroid sulfatase and have been found to ... Ruder, Henry J.; Loriaux, Lynn; Lipsett, M. B. (1972). "Estrone Sulfate: Production Rate and Metabolism in Man". Journal of ...
The metabolic clearance rate of demegestone is 20 L/h. Its biological half-lives are 2.39 and 0.24 hours with intravenous ... Metabolic studies of R2453, a highly potent progestin". Journal of Steroid Biochemistry. 5 (4): 324. doi:10.1016/0022-4731(74) ...
Kono S, Brandon DD, Merriam GR, Loriaux DL, Lipsett MB (January 1981). "Metabolic clearance rate and uterotropic activity of 2- ... or antiestrogenic activity of 2-hydroxyestrone in the uterus may be attributable to an extremely high metabolic clearance rate ...
White BD, Corll CB, Porter JR (1989). "The metabolic clearance rate of corticosterone in lean and obese male Zucker rats". ...
The metabolic clearance rate of estrone is 1,050 L/day/m2 and of estradiol is 580 L/day/m2, while that of estrone sulfate is 80 ... For comparison, the metabolic clearance rate of estriol is 1,110 L/day/m2. A single 1 to 2 mg dose of estrone in oil solution ... The metabolic fate and hepato-biliary-enteric circulation of C14-estrone and C14-estradiol in women". The Journal of Clinical ... The Management of Common Metabolic Bone Disorders. Cambridge University Press. pp. 48-. ISBN 978-0-521-43623-6. Erkkola R (1 ...
The metabolic clearance rate of estriol is approximately 1,110 L/day/m2, which is about twice that of estradiol. Hence, estriol ...
The metabolic clearance rate of progesterone ranges between 2,100 and 2,800 L/day, and is constant across the menstrual cycle. ... and clearance rate (rapid). Vaginal progesterone is available in the forms of progesterone gel, rings, and suppositories or ... The IUD was never widely used due to a relatively high contraceptive failure rate of 2.9% and the requirement of annual ... However, a study found that different manufacturing processes gave different rates of extrusion. Progesterone implants were ...
The metabolic clearance rates of equilin and equilin sulfate are 2,640 L/day/m2 and 175 L/day/m2, respectively. In accordance, ...
The metabolic clearance rate of 17β-dihydroequilin is 1,250 L/day/m2, relative to 580 L/day/m2 for estradiol. 17β- ...
"The Effect of Serum Prolactin on Plasma Adrenal Androgens and the Production and Metabolic Clearance Rate of ... the rates of hepatotoxicity were 15.3% (19 of 124) for flutamide and 9.5% (10 of 105) for CPA (p = 0.034) and the rates of ... the overall rate of depression was 12.7% and the rates did not differ between the two groups. Despite some association with ... Rates of gynecomastia of 4 to 30% have been reported. Galactorrhea (milk outflow) can also occur in men, due to the strong ...
MENT showed a more rapid metabolic clearance rate than T in men and monkeys, probably due in part to its failure to bind SHBG ( ...
These properties of progesterone are thought to be caused by its low water solubility and high metabolic clearance rate due to ... P4-3-CMO could have both improved absorption and increased metabolic stability relative to progesterone. However, the compound ...
... metabolic clearance and basal plasma production rates of testosterone in normal young men and women using a constant infusion ... effect of time of day and plasma concentration on the metabolic clearance rate of testosterone". The Journal of Clinical ... In the final and rate limiting step, the C17 keto group androstenedione is reduced by 17β-hydroxysteroid dehydrogenase to yield ... Kenyon AT, Knowlton K, Sandiford I, Koch FC, Lotwin, G (February 1940). "A comparative study of the metabolic effects of ...
... metabolic clearance rate MeSH G12.091.690.140.600 - metabolic detoxication, drug MeSH G12.091.690.140.600.500 - metabolic ... detoxication, phase i MeSH G12.091.690.140.600.750 - metabolic detoxication, phase ii MeSH G12.091.690.898 - therapeutic ...
... metabolic clearance rate MeSH G06.535.780.202.820 - metabolic detoxication, drug MeSH G06.535.780.202.820.500 - metabolic ... detoxication, phase i MeSH G06.535.780.202.820.750 - metabolic detoxication, phase ii MeSH G06.535.780.559 - therapeutic ...
In mice and rats, both compounds displayed high plasma clearance and short half-lives due to their fast metabolic rates. In a ... Only if the plasma concentration gets higher than 500 ng/mL, an increased heart rate and blood pressure are observed. Although ...
The shared metabolic rate-limiting steps thus leads to slowed metabolism and clearance for both compounds including ethanol's ... which is a metabolic product of 1,4-butanediol. But other Federal courts have ruled that it is not. Butane-1,4-diol is rapidly ...
Fuller JC, Sharp RL, Angus HF, Khoo PY, Rathmacher JA (2015). "Comparison of availability and plasma clearance rates of β- ... "Company Overview of Metabolic Technologies, Inc". Bloomberg. "Studies found for Metabolic Technologies Inc". ClinicalTrials.gov ... Metabolic Technologies is headquartered in Ames, Iowa. The company has sponsored a number of clinical trials for the ... Metabolic Technologies, Inc is an American life sciences company that sells dietary supplements and analytical services. ...
... a rate that is not compatible with the intense metabolic demands of brain tissue. Additionally, a clearance system based on ... The glymphatic system (or glymphatic clearance pathway, or paravascular system) is a system for waste clearance in the central ... they hypothesized that the restorative properties of sleep may be linked to increased glymphatic clearance of metabolic waste ... Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of ...
The systemic clearance [rate] is about 0.2 L/day and the terminal half-life is about 25 days. Pembrolizumab is an ... Since pembrolizumab is cleared from the circulation through non-specific catabolism, no metabolic drug interactions are ... The objective response rate for all patients was 39.6%. Response rates were similar across all cancer types, including 36% in ... By preventing the self-checkpoint system from blocking the T-cells, pembrolizumab appears to facilitate clearance of any such ...
... a health record standard Creatinine clearance rate, a measure of kidney/renal function Crotonyl-CoA carboxylase/reductase, an ... part of the adaptive metabolic control system Chemokine receptor, a term in cell biology Continuity of Care Record, ... an annual water quality report in the United States Corporate credit rating, in investment, a bond credit rating assessing the ... Corinth and Counce Railroad Calculated course rating, a component of the Golf Australia Handicap System Calendar of the Close ...
... plays a special role in the mitochondrial clearance of toxic malonic acid in the metabolic disorder combined ... Malonyl-CoA is a highly regulated molecule in fatty acid synthesis; as such, it inhibits the rate-limiting step in beta- ... "The Mammalian Malonyl-CoA Synthetase ACSF3 Is Required for Mitochondrial Protein Malonylation and Metabolic Efficiency". Cell ...
... because insulin binding antibodies effectively increase the insulin's clearance rate and distribution space and help to prolong ... Due to the relative similarities in structure, proinsulin can produce between 5% and 10% of the metabolic activity similarly ... Postnatal proinsulin is crucial for metabolic regulation. However, proinsulin in neonates is important for normal development ... the focus of many insulin related metabolic diseases has focused on mature insulin. However, in recent years the importance of ...
The rate of removal is significantly increased during sleep. However, the significance of the glymphatic system in Aβ clearance ... The glymphatic system clears metabolic waste from the mammalian brain, and in particular amyloid beta. A number of proteases ... August 2015). "Clearance systems in the brain-implications for Alzheimer disease". Nature Reviews. Neurology. 11 (8): 457-70. ... This is accomplished by promoting microglial clearance and/or redistributing the peptide from the brain to systemic circulation ...
Due to the competition, the rate of mevalonate production by the enzyme is reduced. This also means that the rates subsequent ... In vitro studies with human liver cells showed that two metabolic pathways are equally important; demethylation of the benzylic ... with increased LDL-cholesterol clearance and reduction of both total and LDL cholesterol in the serum. Cerivastatin is ... The reporting rate of fatal rhabdomyolysis in association with cerivastatin monotherapy is 1.9 per million prescriptions, which ...
... which is much greater than the 1 mm/day maximal growth rate as measured for growth cone extension. The rate of 1 mm/day is also ... They are crucial for the metabolic and trophic support of neurons; additionally, astrocytes provide ion buffering and ... neurotransmitter clearance. Growing axons are guided by cues created by astrocytes; thus, astrocytes can regulate neurite ... degradation and resorption rates do not match the tissue formation rate, (2) the stress-strain properties do not compare well ...
... the half-life was approximately 80 minutes and the rate of clearance was 651 ± 221.5 mL/min. Levobupivacaine is an amino-amide ... Metabolic inversion of levobupivacaine is not observed. The extensive metabolism of levobupivacaine by the liver ensures that ... Levobupivacaine has a 97% protein binding rate which is 2% higher than what is observed in bupivacaine. The faster protein ... It is important to adjust the dosage of levobupivacaine in paediatric patients due to their underdeveloped metabolic processing ...
Rate of metabolic cost also follows this relationship. The impact of cadence on leg swing metabolic cost is approximated as E ... and thus increase the metabolic demand. For a narrower stance, due to insufficient clearance, hip torque may be increased to ... is the rate of metabolic cost, W ˙ {\displaystyle \textstyle {\dot {W}}} is the mechanical work rate, and w {\displaystyle \ ... Step width variability is positively correlated with rate of metabolic cost, and with respect to the variability associated ...
Infants born to mothers with high gestational cortisol during the first trimester of pregnancy had lower rates of growth in ... Khani S, Tayek JA (December 2001). "Cortisol increases gluconeogenesis in humans: its role in the metabolic syndrome". Clin Sci ... Drugs that induce CYP3A4 may accelerate cortisol clearance. Cortisol is a naturally occurring pregnane corticosteroid and is ... It also stimulates the main rate-limiting step in cortisol synthesis, in which cholesterol is converted to pregnenolone and ...
"Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate ... it has been suggested that cystatin C might be influenced by the basal metabolic rate. The glomerular sieving coefficients for ... Glomerular filtration rate (GFR), a marker of kidney health, is most accurately measured by injecting compounds such as inulin ... It was first proposed as a measure of glomerular filtration rate by Grubb and coworkers in 1985. Use of serum creatinine and ...
This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the ... This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. ... Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations ... Developing a metabolic clearance rate framework as a translational analysis approach for hyperpolarized 13C magnetic resonance ...
Metabolic Clearance Rate * Molecular Biology * Patient Selection * Phosphodiesterase Inhibitors / immunology * ...
Metabolic Clearance Rate * Procainamide / analogs & derivatives* * Procainamide / pharmacokinetics* * Procainamide / ... We conclude that trimethoprim increases the plasma concentrations of procainamide and NAPA by decreasing their renal clearances ... and NAPA renal clearances after trimethoprim coadministration strongly correlated with their baseline renal clearances (r = ... there was also a trend toward a decrease in the apparent acetylation clearance of procainamide (19%, p = 0.057). The change in ...
Its metabolic clearance rate is 80 L/day/m2. Ovarian tumors have been found to express steroid sulfatase and have been found to ... Ruder, Henry J.; Loriaux, Lynn; Lipsett, M. B. (1972). "Estrone Sulfate: Production Rate and Metabolism in Man". Journal of ...
Surrogate indexes were validated against MLBM/I. ISI, insulin sensitivity index; MCR, metabolic clearance rate; QUICKI, ... A total of 6,414 Finnish men (aged 57 ± 7 years, BMI 27.0 ± 3.9 kg/m2) from our ongoing population-based METSIM (Metabolic ... A total of 6,414 men from the ongoing population-based cross-sectional Metabolic Syndrome in Men (METSIM) study were included ... Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance ...
The metabolic clearance rate of drospirenone in serum is 1.5 ± 0.2 ml/min/kg. Drospirenone is excreted only in trace amounts in ... The metabolite clearance rate of ethinylestradiol is about 5 ml/min/kg. ... Substances increasing the clearance of COCs (diminished efficacy of COCs by enzyme-induction), e.g.: ... Substances decreasing the clearance of COCs (enzyme inhibitors): The clinical relevance of potential interactions with enzyme ...
Metabolic clearance rates may differ between species, meaning teratogenic forms of the drug may not be present for long. ... we know that individuals react differently to drugs and we know individuals have different metabolic rates. Birth defects can ... K. S. Bauer, S. C. Dixon, and W. D. Figg, "Inhibition of angiogenesis by thalidomide requires metabolic activation, which is ... D. Veselá, D. Veselý, and R. Jelínek, "Embryotoxicity in chick embryo of thalidomide hydrolysis products following metabolic ...
Nestler, J. E. and Kahwash, Z. Sex-specific action of insulin to acutely increase the metabolic clearance rate of ... The use of constant infusion of unlabeled dehydroepiandrosterone for the assessment of its metabolic clearance rate, its half- ... each increases the resting metabolic rate of overweight adults. J Nutr Biochem 2007;18:629-634. View abstract. ... Cho, S. H., Choi, M. H., Sim, W. Y., Lee, W. Y., and Chung, B. C. Metabolic alterations of DHEA and cholesterol sulphates in ...
... this leads to a diminished metabolic clearance rate of rT3 and T4. ... The fractional rate of transport of T3 to tissues is unaltered. Production of T3 is decreased, but its clearance is unchanged. ... and the mortality rate was higher, in those suffering from both conditions. For example, the mortality rate during ... Endocrine and metabolic disorders associated with human immune deficiency virus infection. West Afr J Med. 2009 Jan. 28(1):3-9 ...
Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation ... Figure 3: Circulatory Disease Mortality Rates per 100,000 Woman Years by Age, Smoking. Status and Oral Contraceptive Use ... In comparison, average failure rates for other methods of birth control during the first year of use are as follows:. IUD: 0.1- ... The average failure rate of large numbers of pill users is approximately 5% per year (5 pregnancies per 100 women per year of ...
Reasonable care in compiling the information the intake of AAS needs has a faster metabolic clearance rate. ... Tend to be lower in people eating red, cheap order anabolic trace mineral needed for over 300 metabolic processes. Brand name ...
... or metabolic clearance rates within the skin compartments (Bartels, 2021). Relative differences in predicted absorption of the ... Metabolic rate data generated in the in vitro studies above were used to refine the models to more accurately predict behavior ... The initial rate of bis(GSH)-MDI formation (assuming pseudo first order kinetics) with 2,2-, 2,4- and 4,4-MDI in both ... However, as discussed above, the relative reactive dissolution of the NCO presenting molecule in the mixture (i.e. the rate of ...
Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation ... adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical ... 5.7 Adverse Carbohydrate and Lipid Metabolic Effects 5.8 Headache 5.9 Bleeding Irregularities and Amenorrhea 5.10 Depression ... The pregnancy rate (Pearl Index [PI]) in women aged 18-35 years was 1.34 pregnancies per 100 women-years of use (95% confidence ...
Many of these have lower metabolic clearance rates among Chinese, compared with Caucasians, and are prescribed at lower doses ... revealed that the CYP2D6Ch1 allele was the most common one and its distribution correlated well with a higher metabolic ratio ...
IGF binding protein patterns, hence metabolic clearance rates of IGF-I, can be altered by nutrition in neonatal calves (Hammon ... Delaying colostrum intake by one day has important effects on metabolic traits and on gastrointestinal and metabolic hormones ... Metabolic, endocrine and hematological changes in 1-week old calves after milk intake, in response to fasting and during total ... Metabolic and endocrine traits of neonatal calves are influenced by feeding colostrums for different durations or only milk ...
Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for wide individual ... Table 5: Estimated in vivo release rates for Mirena: Time. Estimated in vivo release rate [μg/day] (rounded). ... Release rate of levonorgestrel (LNG) is 21 mcg/day after 24 days; this rate is reduced to about 11 mcg/day after 5 years and 7 ... Mirena contains 52 mg of levonorgestrel (LNG) released in vivo, at a rate of approximately 21 mcg/day after 24 days. This rate ...
1986). Ingestion of a mixed meal does not affect the metabolic clearance rate of biosynthetic human C-peptide. Journal of ... Obesity in the US continues to increase at alarming rates. Diabetes is closely related to obesity, so the increase in obesity ... 1986). Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I ... Insulin and glucagon are two counter regulatory hormones that control the systemic concentration of glucose, a metabolic ...
... habitats may have been characterized by higher clearance rates in contrast to infaunal bivalves with similar metabolic ... Based on actualistic evidence, brachiopods are able to thrive in nutrient-poor conditions due to low metabolic demands and are ... Patterns of longevity and rate of appearance of taxa in the fossil record indicate a different evolutionary dynamic between ... Among marine invertebrates, rates of taxonomic turnover declined through the Phanerozoic, with increasingly extinction- ...
... and increases the metabolic clearance rate of progesterone. Another mechanism of action by which danazol may use to facilitate ... Reduce drug development failure rates. Build, train, & validate machine-learning models. with evidence-based and structured ... With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates ... Mechanism of actionAbsorptionVolume of distributionProtein bindingMetabolismRoute of eliminationHalf-lifeClearanceAdverse ...
The sex-unique metabolic network for steroids is induced neonatally in male rats. The metabolic clearance rates (MCR) of ... Experts rated the simulator as an effective teaching tool, giving it a mean score of 4.22 and 4.44 (maximum, 5) for teaching ... EOIS/THC Score and Volume Deficit are tightly linked to the Hemorrhage Rate. * Remedial actions include Wound care, Volume ... Prenatal testosterone does not exert a crucial role in presetting the peripheral metabolic network in rhesus monkeys. ...
The sex-unique metabolic network for steroids is induced neonatally in male rats. The metabolic clearance rates (MCR) of ... Experts rated the simulator as an effective teaching tool, giving it a mean score of 4.22 and 4.44 (maximum, 5) for teaching ... EOIS/THC Score and Volume Deficit are tightly linked to the Hemorrhage Rate. * Remedial actions include Wound care, Volume ... Prenatal testosterone does not exert a crucial role in presetting the peripheral metabolic network in rhesus monkeys. ...
METABOLIC CLEARANCE RATE, PRODUCTION RATE AND MAMMARY UPTAKE OF PROGESTERONE IN THE GOAT J Endocrinol 64 (3) 485-502, doi: ... METABOLIC EFFECTS OF 2-BROMO ERGOCRYPTINE-METHANE-SULPHONATE (CB 154) IN THE RAT J Endocrinol 64 (3) 587-588, doi: 10.1677/joe. ... METABOLIC PHENOTYPING GUIDELINES: Assessing glucose homeostasis in rodent models. *Vitamin D is crucial for maternal care and ...
Metabolic Clearance Rate. *Neoplasm Proteins. *Polymorphism, Genetic. *Pulmonary Eosinophilia. *Syndrome. *Tacrolimus. *Weight ... FK506 clearance was not influenced by CYP3A5, multidrug resistance 1 or ABCG2 genotypes. None of the clinical parameters ... A time-course study showed that the occurrence of ES, but not acute GVHD, was related to increased clearance of FK506. When ... Engraftment syndrome, but not acute GVHD, younger age, CYP3A5 or MDR1 polymorphisms, increases tacrolimus clearance in ...
Metabolic Clearance Rate; Models, Biological; Rabbits; Sheep; Species Specificity; Swine ...
Metabolic Clearance Rate. -. dc.subject. Polymorphism, Genetic. -. dc.subject. Stereoisomerism. -. dc.subject. Chemistry, ... Assuming the same renal clearances for PM patients accounts for approximately 9 and 4% of their median apparent oral clearances ... The renal clearance of PHX enantiomers was not enantioselective and accounted for ,1% of the median apparent oral clearance of ... with higher apparent oral clearances of (-)-than (+)-PHX. Renal clearance, calculated for EM and subsequently assumed for PM, ...
Another possibility is a difference in the adenosine clearance rate among distinct brain regions, where distribution and ... 2015) Metabolic connection of inflammatory pain: pivotal role of a pyruvate dehydrogenase kinase-pyruvate dehydrogenase-lactic ... ACSF or TNAP-I (3 μl, 10 mg/ml) was directly microinjected into the VLPO region for 30 min at a rate of 0.1 μl/min. The results ... C, Microdialysis was performed at a flow rate of 0.5 ml/min with or without photostimulation of the VLPO region for 120 min in ...
  • Concomitant trimethoprim significantly increased the plasma AUC(0-12) of both procainamide and NAPA (63% and 52%, respectively), with concurrent decreases in their renal clearances (47% and 13%, respectively) and a 39% increase in the mean urinary recovery of NAPA (as percentage of procainamide and NAPA recovery). (nih.gov)
  • The change in procainamide and NAPA renal clearances after trimethoprim coadministration strongly correlated with their baseline renal clearances (r = 0.84 and r = 0.74, respectively, p less than 0.0001). (nih.gov)
  • We conclude that trimethoprim increases the plasma concentrations of procainamide and NAPA by decreasing their renal clearances and allowing more conversion of procainamide to NAPA. (nih.gov)
  • Assuming the same renal clearances for PM patients accounts for approximately 9 and 4% of their median apparent oral clearances of (+)- and (-)-PHX, respectively. (edu.au)
  • Adverse carbohydrate and lipid metabolic effects: Monitor glucose in prediabetic and diabetic women taking CAMRESE. (nih.gov)
  • Insulin and glucagon are two counter regulatory hormones that control the systemic concentration of glucose, a metabolic intermediate used by cells as the primary source of energy. (stratech.co.uk)
  • Magnesium promotes peripheral circulation and assists the body with normal clearance of glucose in founder prone animals. (calabasassaddlery.com)
  • While Chromium has been shown to improve glucose clearance by supporting insulin sensitivity. (calabasassaddlery.com)
  • Together these two minerals support glucose uptake by the cell and a normal metabolic rate. (calabasassaddlery.com)
  • Overall, the NCSU research consistently showed low bioavailability of ivermectin in chicken blood, likely due to rapid detoxifcation and clearance from the blood, among other traits, such as high metabolic rate, they said. (modernpoultry.media)
  • Fever in mammals is accompanied by an initially high metabolic rate associated with beneficial immune responses. (cdc.gov)
  • A screen of 15 major human CYP isoforms for metabolic ability with respect to carbofuran metabolism demonstrated that CYP3A4 is the major isoform responsible for carbofuran oxidation in humans. (cdc.gov)
  • Ment 50 has a faster metabolic clearance rate than Testosterone and does not bind to sex hormone binding globulin. (besttestosteronebrands.com)
  • Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans. (wakehealth.edu)
  • This study demonstrates that camel milk during the 1st month of lactation have important effects on clinical, metabolic and endocrine traits. (scialert.net)
  • 2023. "Increasing the Clearance of Protein Bound Solutes by Recirculating Dialysate through Activated Carbon. (stanford.edu)
  • In contrast, MENT more strongly suppressed bone turnover rate. (purerawz.co)
  • Metabolic conversions are therefore required to increase their water-solubility and enable efficient excretion in urine. (saunaabc.com)
  • Molly Detection Rates In Your Urine: How Long Does It Stay? (galaei.org)
  • The detection of molly in urine tests depends heavily on the type of test used as well as other factors such as an individual's metabolic rate and overall health status. (galaei.org)
  • In order to gain a better grasp on the issue at hand, this article will provide an overview of current research regarding Molly detection rates in urine and discuss possible implications for individuals subject to drug testing procedures. (galaei.org)
  • This results in increased rates of metabolism and body heat. (saunaabc.com)
  • Intrinsic clearance rate calculations indicate that HLM are 14-fold less efficient in the metabolism of carbofuran to 3-hydroxycarbofuran than RLM or MLM. (cdc.gov)
  • Normalization of HLM data with the average levels of each CYP in native HLM, indicates that carbofuran metabolism is primarily mediated by CYP3A4 (percent total normalized rate (% TNR)=77.5), although CYP1A2 and 2C19 play ancillary roles (% TNR=9.0 and 6.0, respectively). (cdc.gov)
  • When a bat is confronted by a viral antigen, the proportional increase in metabolism for raising an immune response may be trivial compared to the very large increase in the metabolic costs of flight. (cdc.gov)
  • Obesity in the US continues to increase at alarming rates. (stratech.co.uk)
  • Obesity is well known for causing morbidity, mortality, disability and has been associated to an increasing number of cardiovascular and metabolic comorbidities, such as hypertension and diabetes mellitus (DM). (researchsquare.com)
  • Though carbofuran has a long history of use, there is little information available with respect to its metabolic fate and disposition in mammals. (cdc.gov)
  • The metabolic cost of raising an immune response to experimental stimulation typically results in a general increase of about 10 to 30 percent of resting metabolic rates in a variety of nonvolant small mammals. (cdc.gov)
  • After trimethoprim coadministration, there was also a trend toward a decrease in the apparent acetylation clearance of procainamide (19%, p = 0.057). (nih.gov)
  • The apparent oral clearance of each enantiomer was calculated from their respective AUC rather than from trough concentrations and was enantioselective in both phenotypes, with higher apparent oral clearances of (-)-than (+)-PHX. (edu.au)
  • 1% of the median apparent oral clearance of each enantiomer in EM patients. (edu.au)
  • Mathematical modeling predicted the dependence of solute clearances on the extent to which solutes were taken up by the carbon block and were bound to plasma proteins.RESULTS: By itself, the conventional system provided clearances of the tightly bound solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) of only 18±10 and 19±11 ml/min, respectively (mean±sd). (stanford.edu)
  • This study investigated a novel perfusion formalism and metabolic clearance rate (MCR) model in pre-clinical stroke and in the healthy human brain. (ox.ac.uk)
  • No studies however have tested testing whether increasing the clearance of bound solutes provides clinical benefit. (stanford.edu)
  • Many of these have lower metabolic clearance rates among Chinese, compared with Caucasians, and are prescribed at lower doses for Asian patients. (aspetjournals.org)
  • Patients with intraoperative complications have low success rate (20%) compared to patients without complications (92.3%), p=0.42. (bvsalud.org)
  • Allele-specific polymerase chain reaction analysis of genomic DNA from 90 Chinese individuals revealed that the CYP2D6Ch1 allele was the most common one and its distribution correlated well with a higher metabolic ratio for debrisoquine. (aspetjournals.org)
  • Strains of laboratory mice that are inbred for higher metabolic rates show stronger immune responses to immune challenge with stronger antigen-specific IgM production than strains bred for lower metabolic rates. (cdc.gov)
  • AIMS/HYPOTHESIS: The incretin hormone glucagon-like peptide 1 (GLP-1) has antihyperglycaemic effects, but its therapeutic usefulness is limited by its metabolic instability. (ku.dk)
  • In addition to these effects, it has been linked with physical side effects such as increased heart rate, dehydration, and loss of appetite. (galaei.org)
  • Reasonable care in compiling the information the intake of AAS needs has a faster metabolic clearance rate. (theopeninter.net)
  • Correct and consistent use of methods can result in lower failure rates. (rxlist.com)
  • Tend to be lower in people eating red, cheap order anabolic trace mineral needed for over 300 metabolic processes. (theopeninter.net)
  • Practical means to increase the dialytic clearance of bound solutes are required to perform such studies.METHODS: Artificial plasma was dialyzed using two dialysis systems in series. (stanford.edu)
  • Chemical measurements tested the ability of the recirculating system to increase the clearance of selected solutes. (stanford.edu)
  • During flight, bats exhibit a high increase in metabolic rate over the resting metabolic rate of normeothermic, otherwise active bats. (cdc.gov)
  • This increase is estimated to be 15-16- fold, in comparison with the 7-fold increase in metabolic rates of rodents running to exhaustion or the 2-fold increase in metabolic rates of most flying birds. (cdc.gov)
  • Table 2 lists the typical unintended pregnancy rates for users of combination oral contraceptives and other methods of contraception. (rxlist.com)
  • Anavar is an oral steroid which is excellent for enhancing the metabolic rate and lipolysis. (saunaabc.com)
  • Hyperpolarized carbon-13 magnetic resonance imaging is a promising technique for in vivo metabolic interrogation of alterations between health and disease. (ox.ac.uk)
  • This study introduces a formalism for quantifying the metabolic information in hyperpolarized imaging. (ox.ac.uk)
  • A total of 6,414 Finnish men (aged 57 ± 7 years, BMI 27.0 ± 3.9 kg/m 2 ) from our ongoing population-based METSIM (Metabolic Syndrome in Men) study were included. (diabetesjournals.org)
  • p class=\'abstract\'>BACKGROUND: Conventional hemodialysis provides limited clearance of uremic solutes that bind to plasma proteins. (stanford.edu)
  • The absence of intraoperative complications was significantly associated with success rate. (bvsalud.org)
  • Hyponatraemia was interpreted as being secondary to prolonged diarrhoea and vomiting, hypokalaemia to stool losses, metabolic alkalosis to extra cellular compartment contraction and the initial but transient rise in blood pressure to secondary hyperaldosteronism. (who.int)
  • His height and weight were below the 3rd percentile, temperature was 38.7 °C, heart rate 98/min, respiratory rate 30/min, blood pressure 70/50 mmHg, O2 saturation 88% in room air and capillary refill 4 seconds. (who.int)
  • Drug treatments, metabolic rates, bed bug behavior and drug-clearance rates vary under field conditions. (modernpoultry.media)
  • This period may vary due to individual metabolic differences and other environmental factors. (galaei.org)
  • The rate of progression to overt hypothyroidism is estimated to be about 5% per year. (medscape.com)
  • Cela permettra en retour de développer votre masse musculaire, via une production plus importante d'hormone de croissance : la testostérone. (jessilafree.com)
  • Multivariate analysis was done to determine factors affecting stone clearance and success rate. (bvsalud.org)
  • The detection rate depends on several factors such as the amount ingested, how long ago it was used, and individual characteristics. (galaei.org)
  • 1994). The formation of ureas is the typical reaction of MDI in aqueous environments, and reaction rates for both MDI and TDI have been shown to be similar (Allport et al. (europa.eu)