Assessment of drug–drug interactions between voriconazole and glucocorticoids

Voriconazole is used to treat fungal infections in patients receiving glucocorticoid therapy in clinic. The objective of this study was to characterize the potential drug–drug interactions (DDIs) between voriconazole and glucocorticoids using physiologically based pharmacokinetic (PBPK) models. Voriconazole and glucocorticoids PBPK models were constructed by using physicochemical data and pharmacokinetic parameters in healthy subjects, and verified by comparing the predicted pharmacokinetic parameters with corresponding data acquired from published literatures. The refined PBPK models were employed to predict the potential DDIs between voriconazole and glucocorticoids. The results showed that the maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from 0 h to infinity (AUC0→inf) of dexamethasone were increased by 2.44-fold and 2.60-fold when combined with voriconazole, respectively. For methylprednisolone, the Cmax and AUC0→inf were increased by 1.56-fold and 2.23-fold, respectively. Our results indicate that the dose of dexamethasone or methylprednisolone can be reduced to maintain approximately similar exposures when used concomitantly with voriconazole.