Assessment of drug–drug interactions between voriconazole and glucocorticoids

Abstract

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 (C_max) and the area under the plasma concentration-time curve from 0 h to infinity (AUC_0→inf) of dexamethasone were increased by 2.44-fold and 2.60-fold when combined with voriconazole, respectively. For methylprednisolone, the C_max and AUC_0→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.

Keywords:

• Voriconazole
• Glucocorticoids
• Drug‐drug interaction
• Physiologically based pharmacokinetics

Disclosure statement

A disclosure statement reporting no conflict of interest has been inserted. Please correct if this is inaccurate.

Notes on contributors

Mengxue Li participated in the design of the study, collection data, statistical analysis and drafted the manuscript.

Lu Chen and Na Li participated in the collection data. Fang Qi participated in the statistical analysis. All authors read and approved the final manuscript.