In vitro and in vivo drug interactions involving human CYP3A

Annu Rev Pharmacol Toxicol. 1998:38:389-430. doi: 10.1146/annurev.pharmtox.38.1.389.

Abstract

Cytochrome P4503A (CYP3A) is importantly involved in the metabolism of many chemically diverse drugs administered to humans. Moreover, its localization in high amounts both in the small intestinal epithelium and liver makes it a major contributor to presystemic elimination following oral drug administration. Drug interactions involving enzyme inhibition or induction are common following the coadministration of two or more CYP3A substrates. Studies using in vitro preparations are useful in identifying such potential interactions and possibly permitting extrapolation of in vitro findings to the likely in vivo situation. Even if accurate quantitative predictions cannot be made, several classes of drugs can be expected to result in a drug interaction based on clinical experience. In many instances, the extent of such drug interactions is sufficiently pronounced to contraindicate the therapeutic use of the involved drugs.

Publication types

  • Review

MeSH terms

  • Aryl Hydrocarbon Hydroxylases*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Oxidoreductases, N-Demethylating / antagonists & inhibitors
  • Oxidoreductases, N-Demethylating / metabolism*
  • Pharmaceutical Preparations / metabolism*
  • Substrate Specificity

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating