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Orally administered drugs are subject to a number of barriers impacting bioavailability (F oral ), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT Keywords:Physiologically-based pharmacokinetics (PBPK); modelling and simulation (M&S); absorption; oral bioavailability (F oral ); biopharmaceutics; drug database Abbreviations

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