Prediction of Intestinal First-Pass Drug Metabolism

Author(s): Jiansong Yang, Masoud Jamei, Karen Rowland Yeo, Geoffrey T. Tucker, Amin Rostami-Hodjegan.

Journal Name: Current Drug Metabolism

Volume 8 , Issue 7 , 2007

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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 “QGut” model. The former overpredicts the fraction escaping first-pass gut metabolism; the latter improves the predictions by accounting for interplay between permeability and metabolism.

Keywords: First-pass metabolism, gut metabolism, CYP3A, P-glycoprotein, drug transport, well-stirred model

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Article Details

Year: 2007
Page: [676 - 684]
Pages: 9
DOI: 10.2174/138920007782109733
Price: $58

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