Drug-drug interactions during antiviral therapy for chronic hepatitis C.
Drug-drug interactions during antiviral therapy for chronic hepatitis C.
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DOI：
10.1038/nrgastro.2013.106
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Everson GT
中科院分区：
文献类型：
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作者：
Kiser JJ;Burton JR Jr;Everson GT
针对HCV感染的直接作用抗病毒药物（DAAs）的出现代表了治疗方面的重大进展。NS3蛋白酶抑制剂boceprevir和telaprevir是首批获得监管机构批准的daa。当与PEG-IFN和利巴韦林联合使用时，这些药物将HCV基因型1的持续病毒学应答率提高到~70%。然而，这种治疗方案与几种毒性有关。此外，boceprevir和telaprevir都是药物转运体p -糖蛋白和细胞色素P450酶3A4的底物和抑制剂，因此容易发生临床相关的药物相互作用。几种新的HCV daa正处于临床开发后期，可能在不久的将来获得批准。这些药物包括蛋白酶抑制剂西莫普韦和法达韦，NS5A抑制剂daclatasvir和核苷酸聚合酶抑制剂sofosbuvir。在此，我们回顾了博昔韦韦、特拉韦和这些研究性daa的临床药理学和药物相互作用。虽然boceprevir和telaprevir涉及许多相互作用，但如果卫生保健提供者主动识别和调整治疗，这些相互作用是可控的。新出现的daa似乎降低了药物相互作用的可能性，这将有助于它们在HCV治疗中的应用。
The emergence of direct-acting antiviral agents (DAAs) for HCV infection represents a major advance in treatment. The NS3 protease inhibitors, boceprevir and telaprevir, were the first DAAs to receive regulatory approval. When combined with PEG-IFN and ribavirin, these agents increase rates of sustained virologic response in HCV genotype 1 to ~70%. However, this treatment regimen is associated with several toxicities. In addition, both boceprevir and telaprevir are substrates for and inhibitors of the drug transporter P-glycoprotein and the cytochrome P450 enzyme 3A4 and are, therefore, prone to clinically relevant drug interactions. Several new DAAs for HCV are in late stages of clinical development and are likely to be approved in the near future. These include the protease inhibitors, simeprevir and faldaprevir, the NS5A inhibitor, daclatasvir, and the nucleotide polymerase inhibitor, sofosbuvir. Herein, we review the clinical pharmacology and drug interactions of boceprevir, telaprevir and these investigational DAAs. Although boceprevir and telaprevir are involved in many interactions, these interactions are manageable if health-care providers proactively identify and adjust treatments. Emerging DAAs seem to have a reduced potential for drug interactions, which will facilitate their use in the treatment of HCV.