Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing to 1/3 in voriconazole package insert seems not be satisfactory clinical practice. In vitro studies demonstrated that the magnitude inhibition depends on voriconazole, while exposure is determined by genotype status CYP2C19. CYP2C19 gene polymorphism challenges management drug-drug interactions(DDIs) between and tacrolimus. This work aimed predict impact DDIs using physiologically based pharmacokinetics (PBPK) models. precision developed models was reasonable evaluating pharmacokinetic parameters fold error, such as AUC0-24, Cmax tmax. increased immediately all population. simulated duration disappearance after withdrawal were 146h, 90h 66h poor metabolizers (PMs), intermediate (IMs) extensive metabolizers(EMs), respectively. optimized PBPK this study can applied assit dose adjustment for with without voriconazole.