Intestinal first-pass metabolism of CYP3A4 substrates

Drug Metab Pharmacokinet. 2008;23(2):87-94. doi: 10.2133/dmpk.23.87.


Cytochrome P450 3A4 (CYP3A4) is present not only in the liver but also in the small intestine, where it functions as a barrier against xenobiotics. Some CYP3A4 substrates exhibit low bioavailability due to intestinal first pass metabolism. The AUCs of such CYP3A4 substrates are remarkably changed by the inhibition, induction, and saturation of CYP3A4 and so prediction of intestinal first-pass metabolism is important. In this article, factors affecting intestinal first-pass metabolism of drugs are reviewed, focusing on the intestinal metabolism by CYP3A. The methods to predict intestinal first-pass metabolism are also reviewed.

Publication types

  • Review

MeSH terms

  • Animals
  • Area Under Curve
  • Beverages
  • Citrus paradisi
  • Cytochrome P-450 CYP3A / physiology*
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Induction
  • Humans
  • Intestinal Mucosa / metabolism*


  • Cytochrome P-450 CYP3A Inhibitors
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human