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Downloads: Evolution of a Detailed Physiological Model to Simulate the Gastrointestinal Transit and Absorption

Downloads Home > Journal papers > Evolution of a Detailed Physiological Model to Simulate the Gastrointestinal Transit and Absorption

Evolution of a Detailed Physiological Model to Simulate the Gastrointestinal Transit and Absorption

To enable more precise prediction of oral drug absorption, an existing physiologically based absorption model was revised. The revised model reflects detailed knowledge of human gastrointestinal (GI) physiology including fluid secretion and absorption, and comprises an elaborate representation of the intestinal mucosa. The alimentary canal from the stomach to the rectum was divided into 12 compartments. A mucosal compartment was added to each luminal segment of the intestine. A training set of 111 passively absorbed drugs with reported fractions of dose absorbed was used to optimize the semiempirical equation, which calculates intestinal permeability coefficients. The model was subsequently integrated into an established physiologically based pharmacokinetic software and validated by prediction of plasma concentration–time profiles of eight test compounds with diverse physicochemical properties. A good correlation between the simulated and experimental fractions of dose absorbed was established for the 111 compounds in the training set. Subsequently, the concentration–time profiles of six out of eight test compounds were predicted with high accuracy. The detailed model for GI transit and absorption presented in this study can help to understand the complex processes of oral absorption better and will be useful during the drug development process. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:5324–5345, 2011

09. January 2014 13:43
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