Decreased tacrolimus plasma concentrations during HCV therapy: a drug-drug interaction or is there an alternative explanation?
Decreased tacrolimus plasma concentrations during HCV therapy: a drug-drug interaction or is there an alternative explanation?
复制标题
DOI：
10.1016/j.ijantimicag.2016.12.004
复制
发表时间：
2017-03-01
影响因子：
10.8
通讯作者：
Burger, D. M.
中科院分区：
文献类型：
--
作者：
Smolders, E. J.;Pape, S.;Burger, D. M.
慢性丙型肝炎病毒（HCV）感染可导致严重的肝硬化，肝移植是唯一的治疗方法。为了防止器官排斥，移植患者接受免疫抑制剂治疗。我们描述了两例接受他克莫司治疗的移植患者，他们同时接受直接作用抗病毒药物（DAAs）治疗慢性HCV感染。他克莫司与所选DAAs之间没有药代动力学相互作用（ddi）。然而，在这两名患者中，他克莫司的血浆浓度在HCV治疗期间下降。我们假设血浆浓度降低不是由DDI引起的，而是HCV感染清除的间接结果。在慢性HCV感染期间，促炎细胞因子可能抑制细胞色素P450 （CYP）酶，CYP酶主要负责他克莫司代谢。如果这是真的，那么随着病毒的清除，这些酶的活性将恢复正常，他克莫司的代谢将增加。这些变化与临床相关，因为他克莫司的剂量需要调整。因此，医生应该意识到，在使用DAAs治疗HCV时，治疗范围窄的CYP底物可能需要调整剂量。(C) 2017 Elsevier B.V.和国际化学疗法学会。版权所有。
Chronic hepatitis C virus (HCV) infection can cause severe liver cirrhosis, for which liver transplantation is the only therapy. To prevent organ rejection, transplanted patients are treated with immunosuppressive agents. We describe two transplanted patients treated with tacrolimus who were simultaneously treated with direct-acting antivirals (DAAs) for their chronic HCV infection. No pharmacokinetic drug-drug interactions (DDIs) were expected between tacrolimus and the selected DAAs. However, in both patients, tacrolimus plasma concentrations decreased during HCV treatment. We hypothesise that decreased plasma concentrations were not caused by a DDI but were an indirect result of the clearance of the HCV infection. During chronic HCV infection, pro-inflammatory cytokines may inhibit cytochrome P450 (CYP) enzymes, which are primarily responsible for tacrolimus metabolism. If this is true, then with clearance of the virus the activity of these enzymes will normalise and tacrolimus metabolism will increase. These changes were clinically relevant because the tacrolimus dosage needed to be adjusted. Therefore, physicians should be aware that CYP substrates with narrow therapeutic ranges might require dose adaption during HCV therapy with DAAs. (C) 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.