In vitro-in vivo extrapolation (IVIVE) for predicting human intestinal absorption and first-pass elimination of drugs: principles and applications.

Oral administration remains the preferred dosing method in clinical practice and drug development. Oral bioavailability (F) is a function of the fraction absorbed (Fabs), gastrointestinal or gut wall availability (FG), and hepatic availability (FH). Therefore, predicting intestinal absorption (Fabs) and first-pass elimination (FG and FH) from in vitro data may facilitate the selection of more orally bioavailable drug candidates in earlier stages of drug discovery and development. This review provides an overview of the determinants of intestinal absorption and first-pass elimination of drugs and focuses on the principles and applications of conventional in vitro--in vivo extrapolation (IVIVE) methods to predict Fabs, FG, and FH in humans.