Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients
Discontinuation of oral amphotericin B therapy does not influence the pharmacokinetics of tacrolimus in heart transplant patients
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DOI：
10.5414/cp204005
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发表时间：
2021-08-01
影响因子：
0.8
通讯作者：
Fukushima, Norihide
中科院分区：
文献类型：
--
作者：
Ikura, Megumi;Nakamura, Tsutomu;Fukushima, Norihide
目的：两性霉素 B (AMPH-B) 用于预防心脏移植 (HTx) 后与免疫抑制治疗相关的机会性感染，同时仔细控制他克莫司 (TAC) 的血药浓度。尽管在体外研究中AMPH-B具有抑制TAC代谢的潜力，但其与临床使用的AMPH-B口服混悬液的相互作用尚未被研究。在本研究中，我们检查了口服 AMPH-B 疗法是否影响 HTx 患者中 TAC 的药代动力学。材料和方法：在日本国立脑心血管中心进行了一项回顾性研究。参与该研究的所有 HTx 患者均接受标准三药免疫抑制治疗，包括定期释放 TAC、吗替麦考酚酯和泼尼松龙，以及 AMPH-B 口服混悬液的预防性治疗。从电子病历系统收集患者特征和临床实验室数据。 TAC 的血液浓度用于药代动力学分析。结果：共有 14 名患者纳入研究。在停止口服 AMPH-B 治疗之前和之后，除了血清肌酐水平和 eGFR 之外，其他变量没有统计学上的显着差异。 TAC 的剂量和谷浓度以及时间-浓度曲线下面积以及根据其浓度计算的表观口服清除率不受 AMPH-B 治疗终止的影响。结论：AMPH-B 口服混悬液预防性治疗不影响 TAC 的药代动力学，并被证明是预防早期 HTx 后真菌感染的安全且简便的方法。
Objective: Amphotericin B (AMPH-B) is used to prevent opportunistic infections associated with immunosuppressive therapy after heart transplantation (HTx), while the blood concentrations of tacrolimus (TAC) are carefully controlled. Although AMPH-B has the potential to inhibit TAC metabolism in in vitro studies, its interaction with clinically used AMPH-B oral suspension has not been investigated. In the present study, we examined whether oral AMPH-B therapy influences the pharmacokinetics of TAC in HTx patients. Materials and methods: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. All patients with HTx enrolled in the study received standard triple-drug immunosuppression therapy including the regular release of TAC, mycophenolate mofetil, and prednisolone as well as prophylactic therapy with AMPH-B oral suspension. Patient characteristics and clinical laboratory data were collected from the electronic medical record system. Blood concentrations of TAC were used for pharmacokinetic analysis. Results: A total of 14 patients were enrolled in the study. There were no statistically significant differences in the variables except for serum creatinine levels and eGFR before and after discontinuation of oral AMPH-B therapy. The dose and trough concentrations of TAC and the area under the time-concentration curve and apparent oral clearance calculated from its concentrations were not influenced by discontinuation of AMPH-B treatment. Conclusion: The prophylactic treatment with AMPH-B oral suspension did not influence the pharmacokinetics of TAC and was demonstrated as a safe and easy method to prevent early post-HTx fungal infection.