Functional interaction of intestinal CYP3A4 and P-glycoprotein

Fundam Clin Pharmacol. 2004 Dec;18(6):621-6. doi: 10.1111/j.1472-8206.2004.00291.x.


Intestinal CYP3A4-mediated biotransformation and active efflux of absorbed drug by P-glycoprotein are major determinants of bioavailability of orally administered drugs. The hypothesis that CYP3A4 and P-glycoprotein may act in concert to limit oral drug bioavailability is attractive from a theoretical point of view. Evidence in support of such an interplay between CYP3A4 and P-glycoprotein comes mainly from a limited number of in vitro and animal studies. Obviously, it is a challenging task to demonstrate in vivo in humans that the function of CYP3A4 and P-glycoprotein in enterocytes is complementary, and results to directly support this concept remain elusive. However, CYP3A4 and P-glycoprotein are clearly an integral part of an intestinal defence system to protect the body against harmful xenobiotics, and drugs that are substrates of both proteins often have a low bioavailability after oral administration. The functional interaction of intestinal CYP3A4 and P-glycoprotein warrants additional study. Further understanding this interplay would be potentially useful during drug development to solve bioavailability problems of new drug entities.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Administration, Oral
  • Animals
  • Biological Availability
  • Clinical Trials as Topic
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / physiology*
  • Enterocytes / metabolism
  • Humans
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism*
  • Intestines / enzymology
  • Models, Animal
  • Pharmacokinetics*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human