The prediction of drug-glucuronidation parameters in humans: UDP-glucuronosyltransferase enzyme-selective substrate and inhibitor probes for reaction phenotyping and in vitro-in vivo extrapolation of drug clearance and drug-drug interaction potential

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    Abstract

    Major advances in the characterization of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) enzyme substrate and inhibitor selectivities and the development of experimental paradigms to investigate xenobiotic glucuronidation in vitro now permit the prediction of a range of drug-glucuronidation parameters in humans. In particular, the availability of substrate and inhibitor "probes" for the major hepatic drug metabolizing UGTs together with batteries of recombinant enzymes allow the reaction phenotyping of drug glucuronidation reactions. Additionally, in vitro experimental approaches and scaling strategies have been successfully applied to the quantitative prediction of in vivo clearance via glucuronidation and drug-drug interaction potential.

    Original languageEnglish
    Pages (from-to)196-208
    Number of pages13
    JournalDrug Metabolism Reviews
    Volume42
    Issue number1
    DOIs
    Publication statusPublished - Feb 2010

    Keywords

    • Clearance prediction
    • Drug-drug interaction
    • Glucuronidation
    • In vitro-in vivo extrapolation
    • Inhibitor probe
    • Reaction phenotyping
    • Substrate probe
    • UDP-glucuronosyltransferase

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