Experimental models for predicting drug absorption and metabolism.

INTRODUCTION: For orally administered drugs, their intestinal absorption and hepatic metabolism are key players for determining a drug's systemic bioavailability and thus therapeutic effect. Drug absorption and metabolism are both complicated processes, with many physicochemical and physiological factors involved. Understanding the contribution of each of these processes is essential in regulating a drug's level in the bloodstream and in maintaining its optimum therapeutic outcome and safety. Several animal models have been established for studying the intestine and liver as barriers to drug delivery and systemic bioavailability. AREAS COVERED: This review provides an overview of available animal and cell-based models that have been used to characterize and predict drug intestinal absorption and hepatic clearance in humans. Among the most commonly used models to study drug intestinal absorption are in-vitro Caco-2 cells, in situ rat intestinal perfusion and the in vivo animal models. On the other hand, hepatic clearance is mostly studied using in vitro techniques. The authors also review in silico approaches which play significant role during early pharmaceutical research. EXPERT OPINION: The current models developed have greatly contributed to our knowledge of drug interactions with physiological factors, while also useful in the prediction of drug intestinal absorption and metabolism. However, much work remains in this area for the successful extrapolation of in vitro-in vivo data and in furthering the development of reliable and accurate models.