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Purpose:  The drug-drug interactions (DDIs) of tacrolimus greatly contributed to pharmacokinetic variability. Nifedipine, frequently prescribed for hypertension, is a competitive CYP3A5 inhibitor which can inhibit tacrolimus metabolism. The objective of this study was to investigate whether CYP3A5 genotype could influence tacrolimus-nifedipine DDI in Chinese renal transplant patients.    Method:  All renal transplant patients were divided into  CYP3A5*3/*3  homozygotes (group I) and  CYP3A5*1  allele carriers ( CYP3A5*1/*1  +  CYP3A5*1/*3 ) (group II). Each group was subdivided into patients taking tacrolimus co-administered with nifedipine (CONF) and that administrated with tacrolimus alone (Controls). Tacrolimus trough concentrations (C 0 ) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C 0 ) (C 0 /D) between CONF and Controls in group I and II, respectively. At the same time, a multivariate line regression analysis was made to evaluate the effect of variates on C 0 /D.    Results:  In this study, a significant DDI between tacrolimus and nifedipine with respect to the  CYP3A5*3  polymorphism was confirmed. In group I ( n  = 43), the C 0 /D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg);  p  = 0.002]. However, this difference was not detected in group II ( n  = 27) ( p  = 0.216). The co-administrated nifedipine and  CYP3A5*3/*3  homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis.    Discussion:  A CYP3A5 genotype-dependent DDI was found between tacrolimus and nifedipine. Therefore, personalized therapy accounting for CYP3A5 genotype detection as well as therapeutic drug monitoring are necessary for renal transplant patients when treating with tacrolimus and nifedipine.

CYP3A5 Genotype-Dependent Drug-Drug Interaction Between Tacrolimus and Nifedipine in Chinese Renal Transplant Patients