Implications of finding synergic in vitro drug-drug interactions between interferon-alpha and ribavirin for the treatment of hepatitis C virus.
Implications of finding synergic in vitro drug-drug interactions between interferon-alpha and ribavirin for the treatment of hepatitis C virus.
复制标题
发现干扰素-α和利巴韦林之间协同体外药物相互作用对治疗丙型肝炎病毒的意义。
DOI：
10.1093/jac/dkh126
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Buckwold,VictorE
中科院分区：
文献类型：
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作者：
Buckwold,VictorE
丙型肝炎病毒（HCV）感染目前使用干扰素-α（IFN-α）和利巴韦林（RBV）的组合来治疗。如果单独使用IFN-α，持续病毒学应答（SVR）率为1.20%，而单独使用RBV时不会导致SVR。然而，当IFN-α和RBV一起使用时，组合导致约40%的SVR率。这种临床协同作用被认为是由于RBV的直接抗病毒作用，或由于RBV刺激免疫应答的间接作用。这两种假设的证据都是有限的。最近，我们进行了anin vitrodrug-drug组合分析，使用HCV复制的替代模型系统，发现在生理相关的药物浓度下，两种药物之间的抗病毒作用具有可重复的协同作用。我们的研究结果提供了实验支持的论点，这些药物的抗病毒活性的直接影响是负责的临床协同作用观察到的患者。
Hepatitis C virus (HCV) infections are currently treated using a combination of interferon-α (IFN-α) and ribavirin (RBV). If IFN-α is utilized alone, the sustained virological response (SVR) rate is ∼20%, whereas when RBV is used alone it does not lead to an SVR. However, when IFN-α and RBV are used together, the combination leads to an SVR rate of ∼40%. This clinical synergy is thought to be due to the direct antiviral effects of RBV, or to indirect effects of RBV that stimulate the immune response. Evidence for either hypothesis is limited. Recently, we undertook anin vitrodrug–drug combination analysis using surrogate model systems of HCV replication and found a reproducible synergy of antiviral effects between the two drugs at physiologically relevant drug concentrations. Our findings provide experimental support for the contention that the direct effects of these drugs’ antiviral activity are responsible for the clinical synergy observed in patients.