Effects of voriconazole on pharmacokinetics of tacrolimus in renal transplantation recipients / 中华器官移植杂志

ABSTRACT

Objective@#To explore the interactions between voriconazole (VRC) and tacrolimus (Tac) in renal transplant recipients, provide dosing rationales for the clinical co-application of two drugs.@*Methods@#Based upon to the inclusion criteria, 17 renal transplantation recipients were selected from August 2012 to December 2016. Before taking VRC, Tac was prescribed for more than 2 days and a steady blood drug concentration was obtained, Tac trough concentrations were determined after using VRC at Day 3/5/7. The pharmacokinetic changes of Tac were analyzed after combined use of VRC.@*Results@#Among them, C0 and C0/D of Tac were significantly higher than those of VRC and inter-group differences were statistically significant. At Day 3, 5 and 7 of co-application, pharmacokinetic results showed that, at Day 7 of VRC dosing, Tac achieved a steady effective concentration of 3-8 μg/L. And the total reduction of Tac was 40%-100% of original dose.@*Conclusions@#In renal transplant recipients, VRC has a significant impact on Tac. Such an effect shows obvious differences between individuals because of nonlinear pharmacokinetics of VRC and path of interaction CYP3A4/CYP3A5 gene polymorphism. During co-application of VRC and Tac, drug concentration of Tac should be monitored regularly and its dosage adjusted accordingly. Individualized dosing is recommended.