Sprycel® (Dasatinib) is a BCS II weakly basic drug that exhibits strong pH dependent solubility. Dasatinib is currently presented in two drug product formulations as an adult immediate release tablet and a pediatric powder for oral suspension (PFOS). A bioequivalence study comparing the formulations in adult healthy subjects found overall exposure (AUC0-24) from suspension treatments was ∼9-13% lower, Cmax was similar, and median Tmax from PFOS was ∼30 minutes earlier. To understand the mechanism contributing to this behavior a combination of biorelevant dissolution studies and physiologically based pharmacokinetic (PBPK) modeling was used to simulate in vivo performance. In-vitro biorelevant dissolution confirmed the rate and extent of release was similar between tablet and suspension formulations (>90% release within first 15 minutes). PBPK parameter sensitivity analysis demonstrated particular sensitivity to dosage form gastric residence time. A 12% higher AUC0-24 was simulated for tablet dosage forms with 10-15 minutes longer gastric transit relative to solutions or suspensions of small particulates (rapid gastric emptying). The corresponding narrow simulated Cmax range also agreed with observed tablet and suspension bioequivalence data. The unique physicochemical properties, absorption characteristics, and inherent differences in dosage form transit behavior are attributed to influence the dasatinib bioequivalence.