PBPK Modeling of Vismodegib: Deconvoluting the Impact of Saturable Plasma Protein Binding, pH-dependent Solubility and Nonsink Permeation

Introduction: Vismodegib displays unique pharmacokinetic characteristics including saturable plasma protein binding to alpha-1 acid glycoprotein (AAG) and apparent time-dependent bioavailability leading to non-linear PK with dose and time, significantly faster time to steady-state and lower than predicted accumulation. Objectives: Given these unique characteristics, a PBPK model was developed to explore mechanistic insights into saturable protein […]