Department of Pharmacy Practice, School of Pharmacy Worcester/Manchester, Massachusetts College of Pharmacy and Health Sciences, Worcester, MA, USA.
Ann Pharmacother. 2011 Sep;45(9):1085-93. doi: 10.1345/aph.1P744. Epub 2011 Aug 9.
To review the pharmacology, pharmacokinetics, safety, and efficacy of boceprevir, a novel oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor for the treatment of chronic HCV infection, specifically, genotype 1.
A literature search was conducted through MEDLINE and EMBASE (1966-May 2011) using the terms boceprevir and SCH 503034. Data from the package insert, abstracts obtained from conferences, and unpublished Phase 2-3 clinical trials, obtained through clinicaltrials.gov, were also reviewed.
All English-language articles identified from the data sources were evaluated. References from selected articles were used to identify other pertinent citations. Article selection focused on pharmacology, clinical trials, safety analyses, and resistance. Preference was given to human data.
Boceprevir is an oral protease inhibitor that binds to the NS3 protein of HCV, ultimately inhibiting viral intracellular replication. Boceprevir displays linear pharmacokinetics and is rapidly absorbed upon oral administration. In clinical studies of treatment-naïve and treatment-experienced patients, boceprevir, in combination with standard of care (pegylated interferon [Peg-IFN]-α-2b with or without ribavirin) achieved greater sustained viral response (SVR) rates compared to standard of care. Safety analyses showed an increased incidence of adverse effects when boceprevir was used with Peg-IFN-α-2b and ribavirin. The most common adverse events reported include fatigue, headache, nausea, dysguesia, and anemia; the incidence of the latter 2 adverse effects may be increased if boceprevir is added to standard therapy. Additional Phase 2 and 3 studies are currently enrolling participants.
Boceprevir should be used in combination with Peg-IFN-α-2b and ribavirin in the treatment of chronic HCV genotype 1 infection. The improved response rates achieved with that combination will make boceprevir a viable option compared with other developing and approved NS3 protease inhibitors for treatment-naïve and treatment-experienced nonresponders/relapsers. Additional data are needed to clarify the potential for resistance and drug interactions.
综述新型口服丙型肝炎病毒（HCV）非结构 3（NS3）蛋白酶抑制剂博赛泼维的药理学、药代动力学、安全性和疗效，该药用于治疗慢性 HCV 感染，特别是基因型 1。
通过 MEDLINE 和 EMBASE（1966 年-2011 年 5 月）检索了 boceprevir 和 SCH 503034 的相关文献。还检索了药物说明书、会议摘要和通过 clinicaltrials.gov 获得的未发表的 2 期-3 期临床试验的数据。
评估了从资料来源获得的所有英文文章。从选定文章的参考文献中找到了其他相关引文。文章选择主要侧重于药理学、临床试验、安全性分析和耐药性。优先考虑人类数据。
博赛泼维是一种口服蛋白酶抑制剂，可与 HCV 的 NS3 蛋白结合，最终抑制病毒的细胞内复制。博赛泼维的药代动力学呈线性，口服后迅速吸收。在初治和经治患者的临床研究中，与标准治疗（聚乙二醇干扰素[Peg-IFN]-α-2b 联合或不联合利巴韦林）相比，博赛泼维联合治疗可提高持续病毒学应答（SVR）率。安全性分析显示，博赛泼维与 Peg-IFN-α-2b 和利巴韦林联合使用时不良反应发生率增加。报告的最常见不良事件包括疲劳、头痛、恶心、味觉障碍和贫血；如果博赛泼维添加到标准治疗中，后 2 种不良事件的发生率可能会增加。目前正在进行更多的 2 期和 3 期研究。
博赛泼维应与 Peg-IFN-α-2b 和利巴韦林联合用于治疗慢性 HCV 基因型 1 感染。与其他正在开发和批准的 NS3 蛋白酶抑制剂相比，该联合治疗方案可提高应答率，成为初治和经治无应答/复发患者的可行选择。需要更多数据来阐明耐药性和药物相互作用的潜力。
