Inter-subject variability in oral drug absorption is usually reported using bioavailability, which has the components: fraction absorbed (fa), fraction passing the gut wall (fg) and fraction escaping hepatic metabolism (fh). In this study, we sought to separate the absorption (fa∗fg) and elimination (fh) components of bioavailability to study variability of absorption and to investigate the effect of formulations, gastric pH and food on absorption variability.Four compounds from the AstraZeneca database with a range of reported bioavailabilities (high, intermediate 1&2 and low) were selected. First, a disposition model using intravenous data was developed; Second, intrinsic clearance and hence hepatic extraction ratio was estimated based on the “well stirred” model; lastly, the oral data were included to enable estimation of fa∗fg as a separate component to hepatic extraction. Population pharmacokinetic model fitting was undertaken with NONMEM v.7.2.The limiting step in absorption for intermediate 1 was dissolution rate and fa∗fg variability increased under elevated gastric pH (15% vs. 38%, respectively). Absorption of solution formulation intermediate 2 increased by 17% in the presence of food but the prolonged release formulation's absorption didn't differ under fasted or fed state. Variability wasn't affected by food for both formulations (~30%). For the low bioavailable compound, variability decreased when formulated as a prolonged-release formulation (39% vs. 15%).The method described here enables an exploration of drug absorption inter-subject variability using population pharmacokinetics. Implementation of such an approach may aid the formulation design process through a better understanding of the factors affecting oral drug absorption variability.