Immortalization Strategies for Epithelial Cells in Primary Culture

Abstract

Predicting the extent of oral drug absorption can be an important aspect to lead candidate selection during the drug development process. Drug absorption from the intestine is the culmination of a number of steps, including drug dissolution in the gastrointestinal tract (GIT), uptake through the intestinal mucosa, followed by delivery into the systemic circulation. In order to predict the in vivo performance of a drug after oral administration, it is essential that the physiochemical and physiological factors affecting drug absorption are established. The Biopharmaceutical Classification System (BCS) has identified that drug solubility and intestinal permeability are the key biopharmaceutical characteristics impacting on drug uptake from the GIT [3]. The current chapter outlines the theoretical basis for the relationship between intestinal permeabil- ity estimates (Peff) and the fraction of dose absorbed in humans ( fa), and the intestinal perfusion models used for determination of intestinal permeability. In addition, a number of alternative in situ/in vivo intestinal absorption models, which facilitate a more mechanistic evaluation of the impact of intestinal versus hepatic first-pass extraction on limiting the oral bioavailability of drugs, are described. Keywords: