AUTHOR=Zong Huiying , Zhang Yundi , Liu Fengxi , Zhang Xiaoming , Yang Yilei , Cao Xiaohong , Li Yue , Li Anan , Zhou Penglin , Gao Rui , Li Yan 

TITLE=Interaction between tacrolimus and calcium channel blockers based on CYP3A5 genotype in Chinese renal transplant recipients

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1458838

DOI=10.3389/fphar.2024.1458838

ISSN=1663-9812

ABSTRACT=<sec><title>Objective</title><p>To investigate the effect of calcium channel blockers (CCBs) on tacrolimus blood concentrations in renal transplant recipients with different <italic>CYP3A5</italic> genotypes.</p></sec><sec><title>Methods</title><p>This retrospective cohort study included renal transplant recipients receiving tacrolimus-based immunosuppressive therapy with or without CCBs in combination. Patients were divided into combination and control groups based on whether or not they were combined with CCBs, and then further analyzed according to the type of CCBs (nifedipine/amlodipine/felodipine). Propensity score matching was conducted for the combination and the control groups using SPSS 22.0 software to reduce the impact of confounding factors. The effect of different CCBs on tacrolimus blood concentrations was evaluated, and subgroup analysis was performed according to the patients’ <italic>CYP3A5</italic> genotypes to explore the role of <italic>CYP3A5</italic> genotypes in drug-drug interactions between tacrolimus and CCBs.</p></sec><sec><title>Results</title><p>A total of 164 patients combined with CCBs were included in the combination groups. After propensity score matching, 83 patients with nifedipine were matched 1:1 with the control group, 63 patients with felodipine were matched 1:2 with 126 controls, and 18 patients with amlodipine were matched 1:3 with 54 controls. Compared with the controls, the three CCBs increased the dose-adjusted trough concentration (C<sub>0</sub>/D) levels of tacrolimus by 41.61%–45.57% (<italic>P</italic> &lt; 0.001). For both <italic>CYP3A5</italic> expressers (<italic>CYP3A5*1*1</italic> or <italic>CYP3A5*1*3</italic>) and non-expressers (<italic>CYP3A5*3*3</italic>), there were significant differences in tacrolimus C<sub>0</sub>/D between patients using felodipine/nifedipine and those without CCBs (<italic>P</italic> &lt; 0.001). However, among <italic>CYP3A5</italic> non-expressers, C<sub>0</sub>/D values of tacrolimus were significantly higher in patients combined with amlodipine compared to the controls (<italic>P</italic> = 0.001), while for <italic>CYP3A5</italic> expressers, the difference in tacrolimus C<sub>0</sub>/D values between patients with amlodipine and without was not statistically significant (<italic>P</italic> = 0.065).</p></sec><sec><title>Conclusion</title><p>CCBs (felodipine/nifedipine/amlodipine) can affect tacrolimus blood concentration levels by inhibiting its metabolism. The <italic>CYP3A5</italic> genotype may play a role in the drug interaction between tacrolimus and amlodipine. Therefore, genetic testing for tacrolimus and therapeutic drug monitoring are needed when renal transplant recipients are concurrently using CCBs.</p></sec>