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Updated: Jul 10, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Prediction of intestinal first-pass drug metabolism
Jiansong Yang1, Masoud Jamei, Karen Rowland Yeo
1Simcyp Limited, Blades Enterprise Centre, Sheffield, UK. J.Yang@simcyp.com
Abstract:
Despite a lower content of many drug metabolising enzymes in the intestinal epithelium compared to the liver (e.g. intestinal CYP3A abundance in the intestine is 1% that of the liver), intestinal metabolic extraction may be similar to or exceed hepatic extraction. Modelling of events on first-pass through the intestine requires attention to the complex interplay between passive permeability, active transport, binding, relevant blood flows and the intrinsic activity and capacity of enzyme systems. We have compared the predictive accuracy of the "well-stirred" gut model with that of the "Q(Gut)" model. The former overpredicts the fraction escaping first-pass gut metabolism; the latter improves the predictions by accounting for interplay between permeability and metabolism.
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