Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.Vonoprazan is metabolized extensively through CYP3A and is an in vitro time-dependent inhibitor of CYP3A.  A physiologically-based pharmacokinetic (PBPK) model for vonoprazan was also developed using in vitro data, drug- and system-specific parameters, and clinical data and observations from a [14 C] human absorption, distribution, metabolism, and excretion study.  The PBPK model was refined and verified using data from a clinical DDI study with the strong CYP3A inhibitor, clarithromycin, to confirm the fraction metabolized by CYP3A, and the oral midazolam clinical DDI data assessing vonoprazan as a time-dependent inhibitor of CYP3A.  The verified PBPK model was applied to simulate the anticipated changes in vonoprazan exposure due to moderate and strong CYP3A inducers (efavirenz and rifampin, respectively).  PBPK simulations projected a 50% to 80% reduction in vonoprazan exposure when administered concomitantly with moderate or strong CYP3A inducers. 
PBPK
Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.Vonoprazan is metabolized extensively through CYP3A and is an in vitro time-dependent inhibitor of CYP3A. 
PBPK modeling
Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.Vonoprazan is metabolized extensively through CYP3A and is an in vitro time-dependent inhibitor of CYP3A.  A physiologically-based pharmacokinetic (PBPK) model for vonoprazan was also developed using in vitro data, drug- and system-specific parameters, and clinical data and observations from a [14 C] human absorption, distribution, metabolism, and excretion study. 
clinical data
Tiered approach to evaluate the CYP3A victim and perpetrator drug-drug interaction potential for vonoprazan using PBPK modeling and clinical data to inform labeling.Vonoprazan is metabolized extensively through CYP3A and is an in vitro time-dependent inhibitor of CYP3A.  A tiered approach was applied to understand the CYP3A victim and perpetrator drug-drug interaction (DDI) potential for vonoprazan. 
tiered approach