Prediction of Intestinal First-Pass Drug Metabolism

Authors: Yang, Jiansong; Jamei, Masoud; Yeo, Karen R.; Tucker, Geoffrey T.; Rostami-Hodjegan, Amin

Source: Current Drug Metabolism, Volume 8, Number 7, October 2007 , pp. 676-684(9)

Publisher: Bentham Science Publishers

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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 “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

Document Type: Research article

Publication date: 2007-10-01

More about this publication?

Current Drug Metabolism aims to cover all the latest and outstanding developments in drug metabolism and disposition. The journal serves as an international forum for the publication of timely reviews in drug metabolism. Current Drug Metabolism is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments. The journal covers the following areas:

In vitro systems including CYP-450; enzyme induction and inhibition; drug-drug interactions and enzyme kinetics; pharmacokinetics, toxicokinetics, species scaling and extrapolations; P-glycoprotein and transport carriers; target organ toxicity and interindividual variability; drug metabolism and disposition studies; extrahepatic metabolism; phase I and phase II metabolism; recent developments for the identification of drug metabolites and adducts.

Prediction of Intestinal First-Pass Drug Metabolism

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