“…PBPK modelling was carried out using the ADAM (Advanced Dissolution, Absorption, and Metabolism) model, which is available as part of the Simcyp PBPK simulator (Version 18, Release 2). Modelling was carried out in a stepwise fashion using an in vitro-in vivo extrapolation (IVIV_E) of dissolution and solubility, as outlined previously by Pathak et al [25,30] and Hens et al [35] Aqueous and bile micelle-mediated solubility data were estimated using the SIVA (Simcyp In Vitro Analysis) toolkit, using solubility data from Section 2.2.1 and other literature sources [18,25,30]. Initially, the intrinsic solubility and solubility factor were calculated using the experimental pH solubility profile in SIVA.…”