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Acta Pharm Sin B. 2016 Sep;6(5):374-383. Epub 2016 Aug 4.

An update on the role of intestinal cytochrome P450 enzymes in drug disposition.

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Bioimaging, GlaxoSmithKline, King of Prussia, PA 19406, USA.
College of Nanoscale Science, SUNY Polytechnic Institute, Albany, NY 12203 USA.
Wadsworth Center, New York State Department of Health, Albany, NY 12201 USA.


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.


AUC, area under concentration-time curve; Bioavailability; CPR, NADPH-cytochrome P450 reductase; Cytochrome P450; DDI, drug–drug interaction; Drug disposition; Drug metabolism; GFJ, grapefruit juice; IECN, intestinal epithelium-specific Cpr-null; Intestine; LCN, liver-specific Cpr-null; P-gp, P-glycoprotein; P450 (or CYP), cytochrome P450; WT, wide-type

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