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接受第一代丙型肝炎病毒蛋白酶抑制剂治疗的患者体内利巴韦林浓度较高。

Patients treated with first-generation HCV protease inhibitors exhibit high ribavirin concentrations.

作者信息

Bodeau Sandra, Nguyen-Khac Eric, Solas Caroline, Bennis Youssef, Capron Dominique, Duverlie Gilles, Brochot Etienne

机构信息

Department of Pharmacology, Amiens University Medical Center, Amiens, France.

出版信息

J Clin Pharmacol. 2015 May;55(5):517-24. doi: 10.1002/jcph.454. Epub 2015 Feb 4.

Abstract

Anemia is a well-known RBV-related event in HCV therapy which is exacerbated by the addition of telaprevir and boceprevir. This retrospective study evaluated and compared ribavirin exposure and parameters able to influence hemoglobin decrease in a large population of patients treated with dual or triple therapy. Patients on triple therapy had higher ribavirin concentrations at week 12 of treatment (3460 ng/mL vs. 1843 ng/mL; P < .0001). An association was also observed between week 12 eGFR and ribavirin concentration only for patients on triple therapy (P = .002). The proportion of patients with a  >20 mL/min/1.73 m(2) decrease in eGFR at week 12 was higher among patients on triple therapy: 32%, 14%, and 5% for boceprevir, telaprevir, and dual therapy, respectively (P = .025 and .026). No correlation was observed between boceprevir and telaprevir concentrations and hemoglobin or eGFR decrease. Exacerbation of anemia in patients on triple therapy is related to higher ribavirin concentrations. We provide an explanation for this increase in plasma RBV concentration. Triple therapy with PEG-IFN, RBV, and telaprevir or boceprevir will remain the only HCV treatment option for many patients. Our data show that the RBV dose can be decreased while maintaining adequate plasma concentrations and reducing anemia.

摘要

贫血是丙型肝炎病毒(HCV)治疗中一种众所周知的与利巴韦林(RBV)相关的事件,添加特拉匹韦和博赛匹韦会加剧这种情况。这项回顾性研究评估并比较了在接受双重或三重疗法治疗的大量患者中利巴韦林的暴露量以及能够影响血红蛋白下降的参数。接受三重疗法的患者在治疗第12周时利巴韦林浓度更高(3460 ng/mL对1843 ng/mL;P < .0001)。仅在接受三重疗法的患者中还观察到第12周的估算肾小球滤过率(eGFR)与利巴韦林浓度之间存在关联(P = .002)。在接受三重疗法的患者中,第12周时eGFR下降>20 mL/min/1.73 m²的患者比例更高:博赛匹韦、特拉匹韦和双重疗法的患者比例分别为32%、14%和5%(P = .025和.026)。未观察到博赛匹韦和特拉匹韦浓度与血红蛋白或eGFR下降之间存在相关性。接受三重疗法的患者贫血加剧与更高的利巴韦林浓度有关。我们对血浆RBV浓度的这种升高给出了解释。聚乙二醇干扰素(PEG-IFN)、RBV与特拉匹韦或博赛匹韦的三重疗法仍将是许多患者唯一的HCV治疗选择。我们的数据表明,可以降低RBV剂量,同时维持足够的血浆浓度并减少贫血。

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