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 .
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.