Advances and challenges in PBPK modeling - Analysis of factors contributing to the oral absorption of atazanavir, a poorly soluble weak base.

•Atazanavir shows highly variable PK with an unusual behavior for the 100mg dose.•In vitro data were coupled with in silico models to investigate factors of atazanavir variability.•An in silico model was developed to investigate efflux and excretion mechanisms assumed for the 100mg dose.•PK variability of atazanavir is mostly driven by post-absorptive factors.•This work gives insight on whether formulation improvement is feasible for highly variable compounds as atazanavir.