Predicting human drug pharmacokinetics from in vitro permeability using an absorption–disposition model

✍ Scribed by Kyle A. Fliszar; Brian T. Hill; Natalie Foster

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 295 KB
• Volume: 96
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.20866

✦ Synopsis

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 C max , 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 C max 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.