A preliminary exploration of liver microsomes and PBPK to uncover the impact of CYP3A4/5 and CYP2C19 on tacrolimus and voriconazole drug-drug interactions.

ABSTRACT: Solid transplant recipients are at increased risk for invasive aspergillosis. Tacrolimus and Voriconazole is one of the most frequently utilized treatments for those recipients with invasive fungal infections. However, it is difficult to use them properly due to the interaction between them. This study aimed to investigate the potential drug-drug interaction between Tacrolimus and Voriconazole by multiple methods, including in vitro liver microsome method and the PBPK(Physiologically Based Pharmacokinetic) model. Midazolam and testosterone were used as probe substrates to evaluate individual differences in CYP3A4/5 metabolic activity. A comprehensive interaction analysis was also conducted based on the STITCH database and the DD-Inter system. Furthermore, a PBPK model was constructed by th

SUBMITTER: Zhao YC 

PROVIDER: S-EPMC11845724 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature