Zong Huiying, Zhang Yundi, Liu Fengxi, Zhang Xiaoming, Yang Yilei, Cao Xiaohong, Li Yue, Li Anan, Zhou Penglin, Gao Rui, Li Yan
Department of Clinical Pharmacy, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, China.
Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, Jinan, Shandong, China.
Front Pharmacol. 2024 Aug 29;15:1458838. doi: 10.3389/fphar.2024.1458838. eCollection 2024.
To investigate the effect of calcium channel blockers (CCBs) on tacrolimus blood concentrations in renal transplant recipients with different genotypes.
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' genotypes to explore the role of genotypes in drug-drug interactions between tacrolimus and CCBs.
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/D) levels of tacrolimus by 41.61%-45.57% ( < 0.001). For both expressers ( or ) and non-expressers (), there were significant differences in tacrolimus C/D between patients using felodipine/nifedipine and those without CCBs ( < 0.001). However, among non-expressers, C/D values of tacrolimus were significantly higher in patients combined with amlodipine compared to the controls ( = 0.001), while for expressers, the difference in tacrolimus C/D values between patients with amlodipine and without was not statistically significant ( = 0.065).
CCBs (felodipine/nifedipine/amlodipine) can affect tacrolimus blood concentration levels by inhibiting its metabolism. The 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.
探讨钙通道阻滞剂（CCB）对不同基因型肾移植受者他克莫司血药浓度的影响。
本回顾性队列研究纳入接受以他克莫司为基础的免疫抑制治疗且联合或不联合CCB的肾移植受者。根据是否联合CCB将患者分为联合组和对照组，然后根据CCB类型（硝苯地平/氨氯地平/非洛地平）进一步分析。使用SPSS 22.0软件对联合组和对照组进行倾向评分匹配，以减少混杂因素的影响。评估不同CCB对他克莫司血药浓度的影响，并根据患者基因型进行亚组分析，以探讨基因型在他克莫司与CCB药物相互作用中的作用。
联合组共纳入164例联合CCB的患者。倾向评分匹配后，83例使用硝苯地平的患者与对照组1:1匹配，63例使用非洛地平的患者与126例对照组2:1匹配，18例使用氨氯地平的患者与54例对照组1:3匹配。与对照组相比，三种CCB使他克莫司的剂量调整谷浓度（C/D）水平升高41.61% - 45.57%（P < 0.001）。对于表达者（携带者或非携带者）和非表达者，使用非洛地平/硝苯地平的患者与未使用CCB的患者在他克莫司C/D方面存在显著差异（P < 0.001）。然而，在非表达者中，联合使用氨氯地平的患者他克莫司C/D值显著高于对照组（P = 0.001），而对于表达者，使用氨氯地平和未使用氨氯地平的患者在他克莫司C/D值上的差异无统计学意义（P = 0.065）。
CCB（非洛地平/硝苯地平/氨氯地平）可通过抑制他克莫司代谢影响其血药浓度水平。基因型可能在他克莫司与氨氯地平的药物相互作用中起作用。因此，肾移植受者同时使用CCB时，需要进行他克莫司基因检测和治疗药物监测。
