Implications of intercorrelation between hepatic CYP3A4‐CYP2C8 enzymes for the evaluation of drug–drug interactions: a case study with repaglinide

Abstract

The present study demonstrates via a systematic investigation that population-based PBPK modelling incorporating intercorrelation led to more consistent estimation of extreme values than those observed in interindividual variabilities of clearance and DDI. As the intercorrelations more realistically reflect enzyme abundances, virtual population studies involving PBPK and DDI should avoid using Monte Carlo assignment of enzyme abundance.