Comparison of the Static <i>In Vivo</i> Approach to a Physiologically Based Pharmacokinetic Approach for Metabolic Drug–Drug Interactions Prediction

Abstract

Background: The in vivo mechanistic static model (IMSM) and the physiologically based pharmacokinetic (PBPK) model are two approaches used to predict the magnitude of drug–drug interactions (DDIs). The aim of this study was to evaluate the performance of IMSM and to compare IMSM with the PBPK approach implemented in Simcyp. Methods: The predictive performances of IMSM were evaluated on a panel of 628 DDIs. Subsequently, the IMSM and PBPK approaches were compared on a set of 104 DDIs. Results: The IMSM yielded 85% of predictions within 1.5-fold of the observed value on the 628 DDIs panel. The predictive performances of IMSM were better than those of the PBPK approach (median fold error 1 vs 0.86 on 104 studies; p = 0.02). Conclusion: The IMSM approach is an alternative tool for metabolic DDIs prediction.