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Showing 1 to 19 of 19 for “"drug metabolizing enzymes"”.
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The interaction of some halogenated anaesthetic agents with hepatic drug metabolizing enzymes
… methoxyflurane and enflurane, with hepatic drug metabolizing enzymes in vivo and in vitro. Each of the anaesthetic agents interacts with the type P-450 cytochromes of hepatic microsomes in vitro resulting in the appearance of a type I difference spectrum, enhancement of NADPH oxidation and …
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Investigation of ocular drug metabolism and pharmacokinetics using multi-omics and in-situ microdialysis
Ocular drug disposition is governed by a complex interplay of anatomical barriers, local metabolic activity, transporter expression, and tissue-specific physiological processes. However, quantitative understanding of drug-metabolizing enzymes and transporters in ocular tissues remains limited, …
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Investigations on the antifungal and cancer modulating properties of extracts from selected species of Tulbaghia
… rate application. Modulation studies of hepatic drug metabolizing enzymes and oxidative properties of AI/ium sativum, Tulbaghia violacea and T. alliacea in male Fischer rats were also evaluated. Due to its complex phytochemical composition a battery of assays were used to evaluate antioxidant …
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Age-Associated Expression Patterns of OATP 1B1 and OATP 1B3 and Their Effect on the Disposition of Fexofenadine
As part of the drug disposition process (absorption, distribution, metabolism, excretion), an often overlooked aspect is transport. In order for drugs to be metabolized and excreted from the body they go through the liver or other drug removal organs. For drugs that are polar or are large they must …
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Methylome and Transcriptome Profiling of Hepatocytes Derived from Human Pluripotent Stem Cells
… and are extensively used to recapitulate drug metabolism. However, they lack stem cell ability and therefore cannot multiply, and will vary depending on each donator. Toward this, hepatocytes derived from human pluripotent stem cells (hPSC-HEP) recapitulate many features of their in vivo …
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Farnesol-Mediated Regulation Of Hepatic Lipid Metabolism In Heparg Cells
… mRNA levels of several hepatic lipid- and drug-metabolizing enzymes in both control and OA-overloaded HepaRG cells, and the expression pattern was similar to that achieved through activation of PPARα rather than through CAR or FXR. </p> <p> In OA-overloaded HepaRG cells, farnesol treatment …
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Development of a collagen gel sandwich hepatocyte bioreactor for detecting hepatotoxicity of drugs and chemicals
Understanding the hepatotoxicity of drugs and chemicals is essential for progress in academic research, medical science and in the development of new pharmaceuticals. Studying hepatotoxicity in vitro is a challenging task because hepatocytes, the metabolically active cells of the liver, are very …
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Genetic Predictors of Hyperglycemia Due to Hydrochlorothiazide Therapy
… Some patients respond favorably to a drug while others develop adverse reactions. Early investigations showed evidence of variation in genes that code for drug receptors, drug transporters, and drug metabolizing enzymes; and pharmacogenetics appeared as the science that studies the …
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Effect of cell- and species-differences in the expression of drug metabolism enzymes on chemical-induced injury to the rat and human kidney
Differences in the expression of drug metabolizing enzymes between cells of the rat and human kidney on chemical-induced nephrotoxicity were studied. Rat renal proximal tubular (rPT) and distal tubular (rDT) cells differed in their susceptibility to trichloroethylene (Tri) and thiophene-containing …
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Regulation of Hepatic Drug Transporters Expression in Mice During Acute Inflammation
… of several hepatic ABC and SLC transporters and drug-metabolizing enzymes. These pronounced changes in hepatic transporters contribute to altered drug disposition; therefore, understanding the molecular mechanisms would aid in identifying potential sources of drug variability in diseases …
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Nash Alters Drug Metabolizing Enzyme and Transporter Expression Resulting in Significant Consequences for Pharmaceutical Disposition and Toxicity
… The major cellular effectors of ADME are the drug metabolizing enzymes (DMEs) and transporters. DMEs function to transform xenobiotics into a metabolite that is more suitable for excretion, whereas drug transporters serve a two-fold function. They may facilitate the uptake of the xenobiotic …
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Development of genotyping systems for pharmacogenomics profiling
Genetic variability in genes encoding drug metabolizing enzymes, transporters and targets are known to be the main factors of inter-individual differences in therapeutic outcome. Genetic factors are estimated to be responsible for about 15-30% of inter-individual variation in drug disposition and …
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Quantitative pharmacoproteomics investigation of anti-cancer drugs in mouse. Development and optimisation of proteomics workflows for evaluating the effect of anti-cancer drugs on mouse liver
Minimizing anti-cancer drug toxicity is a major challenge for the pharmaceutical industry. Toxicity is most frequently due to either the direct interaction of the drug on previously unidentified targets or its conversion to metabolites by drug metabolizing enzymes (e.g. CYP450 enzymes) that cause …
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IN VITRO AND IN VIVO KINETIC MODELING OF DIAZEPAM METABOLISM
Drug metabolism plays an important role in drug absorption and drug elimination. Therefore, it is crucial to understand the mechanism and kinetics of drug metabolism by various drug-metabolizing enzymes (DMEs). Cytochrome P450 enzymes (CYPs) are responsible for the metabolism of more than 60% of …
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Regulation of Human Renal Drug Transporters by Inflammatory Cytokines and Pregnancy-related Hormones in Primary Proximal Tubular Epithelial Cells
Systemic inflammation and pregnancy both alter drug pharmacokinetics by changing physiology and modulating drug-metabolizing enzymes and transporters in eliminating organs. Regulation of hepatic enzymes in these states is relatively well described. However, the magnitude, direction, and mechanisms …
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INDUCED PLURIPOTENT STEM CELL DERIVED LIVER MODEL FOR THE STUDY OF PNPLA3-ASSOCIATED NON-ALCOHOLIC FATTY LIVER DISEASE
… the PNPLA3KO cells downregulated all phases of drug metabolizing enzymes which made them more susceptible to other forms of hepatotoxicity such as ethanol. The PNPLA3I148M cells exhibited an intermediate phenotype between untargeted and PNPLA3KO cells. These results demonstrate for the first …
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Porcine model of xenobiotic metabolism
… removes xenobiotics by xenobiotic metabolism. Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination, and detoxification of xenobiotics introduced into the body. Orphan nuclear receptors play crucial role in regulation of the expression of DMEs. The pig has quickly …
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Effect of obesity on hepatic drug metabolism
… thesis was to determine the effect of obesity on drug metabolism and evaluate methods that could potentially predict changes in pharmacokinetics in the obese population. The impact of obesity on drug metabolism in children has not been determined and our clinical study (Chapter 2) was the first of …
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Renal Drug Transporters – Clinical Significance and Role in Drug-Drug Interactions
Drug transporters play an important role in drug disposition and can be major determinants of drug pharmacokinetics, pharmacodynamics and toxicity. In contrast to drug metabolizing enzymes, which mainly concentrate in the liver and small intestine, drug transporters are expressed ubiquitously …