The purpose of this research is to simulate the in vivo performance of drugs with a wide range of solubility and permeability characteristics formulated as oral dosage forms. The absorption-disposition model was developed using a number of physiological parameters as well as in vitro permeability data generated with Caco-2 cells, 2/4/A1 cells, and hexadecane membranes. A total of 13 drugs with varying solubility and permeability properties were examined using the absorption-disposition model to predict their pharmacokinetic profile. The correlation of predicted and experimentally determined AUC and Cmax, as measures of the pharmacokinetic profile, were >0.96 for all permeation techniques examined. The predictive ability of the model is influenced by the type of permeation method employed; 2/4/A1 cell data yielded the highest degree of accuracy in predicting Cmax and AUC values. The absorption-disposition model developed in this work accurately predicts the in vivo performance of a wide range of orally administered drugs with 8 of 9 drugs examined falling within 80-125% of the experimental value of AUC when using 2/4/A1 cells.
(c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.