Strategy for Identifying Rational Sensitivity Analysis Using PBPK Modeling for Precipitant Drug–Drug Interaction Predictions

Physiology Based Pharmacokinetic (PBPK) modeling is an established essential tool for predicting and/or analyzing drug-drug interactions (DDI). Uncertainty and variability associated with in vitro determined DDI-related parameters have often been considered a limitation for predicting PBPK-DDIs. Sensitivity analysis (SA) around DDI input parameters using PBPK analysis is often applied for assessing the relevance of clinical DDI predictions/prioritization/study designs. This perspective aims to explore and advocate practical approaches for precipitant (inhibitor/inducer) PBPK-DDI SA for optimal clinically relevant evaluations.