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

Drug Metab Rev. 2010 Feb;42(1):196-208. doi: 10.3109/03602530903210716.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Drug Interactions
  • Glucuronides / metabolism
  • Glucuronosyltransferase / chemistry
  • Glucuronosyltransferase / metabolism*
  • Humans
  • Metabolic Clearance Rate*
  • Microsomes, Liver / enzymology
  • Models, Molecular
  • Molecular Structure
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism
  • Quantitative Structure-Activity Relationship
  • Substrate Specificity*
  • Uridine Diphosphate / chemistry*
  • Xenobiotics / metabolism*

Substances

  • Glucuronides
  • Pharmaceutical Preparations
  • Xenobiotics
  • Uridine Diphosphate
  • Glucuronosyltransferase