Metabolism profiling, and cytochrome P450 inhibition & induction in drug discovery

Curr Top Med Chem. 2001 Nov;1(5):403-25. doi: 10.2174/1568026013395001.


To reduce the high attrition rates of NCEs in preclinical and clinical development uncovering pharmacokinetics, toxicokinetics, drug metabolism, and drug-drug interactions early in drug discovery would be highly valuable. There have been many in vitro screens developed for these areas that have higher sample throughput, which is consistent with the iterative cycle of a typical drug discovery research project. We have presented the present status and given detailed descriptions of biotransformation, metabolic stability assays, identification of drug metabolizing P450 enzymes, prediction of pharmacokinetic parameters from in vitro metabolism data, structure elucidation of metabolites, CYP450 inhibition assays and CYP450 induction assays from a drug discovery perspective. Strategies for the proper sequencing of primary and secondary assays employedfor drug metabolism and CYP450 inhibition & induction is discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / metabolism*
  • Drug Evaluation, Preclinical / methods*
  • Drug Interactions
  • Drug-Related Side Effects and Adverse Reactions
  • Enzyme Induction / drug effects
  • Humans
  • Liver / drug effects
  • Liver / enzymology*
  • Liver / metabolism
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics*


  • Cytochrome P-450 Enzyme Inhibitors
  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System