Fig. 6.

Mechanistic pharmacokinetic-pharmacodynamic simulations integrating abiraterone PK and CYP17A1-abiraterone binding kinetics into eventual predictions of efficacy outcomes. (A) Simulated apparent CYP17A1 occupancy over time plots after a single in vivo dose of 1000 or 500 mg of abiraterone acetate (AA). The clinical plasma concentration-time profiles of abiraterone are represented by open symbols, whereas the solid and dashed lines indicate the predicted percentage apparent CYP17A1 occupancy over time. Time-dependent changes in apparent CYP17A1 engagement were subsequently used to predict potential perturbations in the intracellular concentrations of (B) dehydroepiandrosterone-sulfate after multiple-dose administration of 1000 or 500 mg AA over 72 hours.