AUTHOR=Yang Yilei , Huang Xin , Shi Yinping , Yang Rui , Shi Haiyan , Yang Xinmei , Hao Guoxiang , Zheng Yi , Wang Jianning , Su Lequn , Li Yan , Zhao Wei 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.692922

DOI=10.3389/fphar.2021.692922

ISSN=1663-9812

ABSTRACT=<p><bold>Purpose:</bold> 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.</p><p><bold>Method:</bold> All renal transplant patients were divided into <italic>CYP3A5*3/*3</italic> homozygotes (group I) and <italic>CYP3A5*1</italic> allele carriers (<italic>CYP3A5*1/*1</italic> + <italic>CYP3A5*1/*3</italic>) (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<sub>0</sub>) were measured using high performance liquid chromatography. A retrospective analysis compared tacrolimus dose (D)-corrected trough concentrations (C<sub>0</sub>) (C<sub>0</sub>/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<sub>0</sub>/D.</p><p><bold>Results:</bold> In this study, a significant DDI between tacrolimus and nifedipine with respect to the <italic>CYP3A5*3</italic> polymorphism was confirmed. In group I (<italic>n</italic> = 43), the C<sub>0</sub>/D of CONF was significantly higher than in Controls [225.2 ± 66.3 vs. 155.1 ± 34.6 ng/ml/(mg/kg); <italic>p</italic> = 0.002]. However, this difference was not detected in group II (<italic>n</italic> = 27) (<italic>p</italic> = 0.216). The co-administrated nifedipine and <italic>CYP3A5*3/*3</italic> homozygotes significantly increased tacrolimus concentrations in multivariate line regression analysis.</p><p><bold>Discussion:</bold> 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.</p>