Pharma Focus Asia

An Update On The Role Of Intestinal Cytochrome P450 Enzymes In Drug Disposition

Authors: Fang Xie, Xinxin Ding, Qing-Yu Zhang


Oral administration is the most commonly used route for drug treatment. Intestinal cytochrome P450 (CYP)-mediated metabolism can eliminate a large proportion of some orally administered drugs before they reach systemic circulation, while leaving the passage of other drugs unimpeded. A better understanding of the ability of intestinal P450 enzymes to metabolize various clinical drugs in both humans and preclinical animal species, including the identification of the CYP enzymes expressed, their regulation, and the relative importance of intestinal metabolism compared to hepatic metabolism, is important for improving bioavailability of current drugs and new drugs in development. Here, we briefly review the expression of drug-metabolizing P450 enzymes in the small intestine of humans and several preclinical animal species, and provide an update of the various factors or events that regulate intestinal P450 expression, including a cross talk between the liver and the intestine. We further compare various clinical and preclinical approaches for assessing the impact of intestinal drug metabolism on bioavailability, and discuss the utility of the intestinal epithelium–specific NADPH-cytochrome P450 reductase-null (IECN) mouse as a useful model for studying in vivo roles of intestinal P450 in the disposition of orally administered drugs.


Cytochrome P450; Intestine; Bioavailability; Drug disposition; Drug metabolism

Citation: Fang Xie, Xinxin Ding, Qing-Yu Zhang An Update On The Role Of Intestinal Cytochrome P450 Enzymes In Drug Disposition doi:10.1016/j.apsb.2016.07.012

Received: 28 April 2016, Revised: 12 July 2016, Accepted: 14 July 2016, Available online: 4 August 2016

Copyright: © 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (


This work was supported in part by grants from the U. S. National Institutes of Health (CA092596, ES020867, and GM082978).

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