The Role of the Intestine in Drug Metabolism and Pharmacokinetics: An Industry Perspective

Over the past decade, our knowledge concerning the importance of intestinal metabolism in the disposition of xenobiotics has significantly improved. Compounds such as midazolam can be extensively extracted in the intestine upon first-pass metabolism after oral dosing. Conversely, the intestine plays a less important, albeit less characterized role in systemic metabolism. This manuscript is meant to review the published examples of pharmaceutical industry research on the intestinal metabolism of xenobiotics, including the various in vitro and in vivo models used. While it is clear that some examples exist of published characterization of the role of intestinal metabolism in drug disposition from the pharmaceutical industry, the majority of industry literature ignores its contribution. The opportunity exists to increase the examination of intestinal metabolism of drugs and drug candidates in industry.