title: Evolution of a detailed physiological model to simulate the gastrointestinal transit and absorption process in humans, part 1: oral solutions.
abstract: 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.
authors: Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, 60438 Frankfurt am Main, Germany. kirstin.thelen@bayer.com
authors: Kirstin
authors: K
authors: Thelen
authors: Katrin
authors: K
authors: Coboeken
authors: Stefan
authors: S
authors: Willmann
authors: Rolf
authors: R
authors: Burghaus
authors: Jennifer B
authors: JB
authors: Dressman
authors: Jörg
authors: J
authors: Lippert
mesh_terms: D000284:Administration, Oral; D005772:Gastrointestinal Transit; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D012996:Solutions / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D012996:Solutions