Klibanov Olga M, Gale Stormi E, Santevecchi Barbara
Wingate University School of Pharmacy, Wingate, NC, USA
Wingate University School of Pharmacy, Wingate, NC, USA.
Ann Pharmacother. 2015 May;49(5):566-81. doi: 10.1177/1060028015570729. Epub 2015 Feb 13.
To review the data with ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection.
Phase I, II, and III trials and review articles were identified through MEDLINE (1996-January 2015) and PubMed (1996-January 2015), conference abstracts, and US national clinical trials registry, using the keywords NS3/4A protease inhibitor, NS5A inhibitor, NS5B polymerase inhibitor, ABT-450, ABT-267, ABT-333, paritaprevir, ombitasvir, and dasabuvir.
Preclinical, phase I, II, and III studies describing pharmacology, pharmacokinetics, efficacy, safety, and tolerability were identified.
Noncirrhotic patients with HCV genotype 1b experienced sustained virological response 12 weeks after completion of therapy (SVR12) rates of 96% to 100% when ombitasvir/paritaprevir/ritonavir and dasabuvir were administered for 12 weeks, regardless of inclusion of ribavirin. SVR12 rates of 95% to 97% were seen in noncirrhotic patients with HCV genotype 1a infection who received ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 weeks. Patients with Child-Pugh Class A cirrhosis also experienced high SVR12 rates (91.8%) when ombitasvir/paritaprevir/ritonavir and dasabuvir were administered with ribavirin for 12 weeks. Cirrhotic patients with HCV genotype 1a and a history of prior null response to peginterferon/ribavirin have higher SVR12 rates when ombitasvir/paritaprevir/ritonavir and dasabuvir and ribavirin are administered for 24 instead of 12 weeks (94.2% vs 88.6%). Adverse events are typically mild, most commonly consisting of fatigue, headache, nausea, and diarrhea.
The regimen consisting of ombitasvir/paritaprevir/ritonavir and dasabuvir is highly efficacious in the treatment of HCV genotype 1 infection, with minimal adverse events. It is expected to play an important role in the armamentarium of novel agents that have a high chance of curing HCV infection.
回顾使用奥比他韦/帕利瑞韦/利托那韦和达沙布韦治疗慢性丙型肝炎病毒（HCV）1型感染的数据。
通过MEDLINE（1996年 - 2015年1月）和PubMed（1996年 - 2015年1月）、会议摘要以及美国国家临床试验注册库，使用关键词NS3/4A蛋白酶抑制剂、NS5A抑制剂、NS5B聚合酶抑制剂、ABT - 450、ABT - 267、ABT - 333、帕利瑞韦、奥比他韦和达沙布韦，检索了I期、II期和III期试验及综述文章。
确定了描述药理学、药代动力学、疗效、安全性和耐受性的临床前、I期、II期和III期研究。
HCV 1b型非肝硬化患者在接受奥比他韦/帕利瑞韦/利托那韦和达沙布韦治疗12周后，无论是否联用利巴韦林，12周持续病毒学应答（SVR12）率为96%至100%。HCV 1a型非肝硬化感染患者接受奥比他韦/帕利瑞韦/利托那韦和达沙布韦联合利巴韦林治疗12周时，SVR12率为95%至97%。Child - Pugh A级肝硬化患者在接受奥比他韦/帕利瑞韦/利托那韦和达沙布韦联合利巴韦林治疗12周时，也有较高的SVR12率（91.8%）。HCV 1a型且既往对聚乙二醇干扰素/利巴韦林无应答史的肝硬化患者，接受奥比他韦/帕利瑞韦/利托那韦、达沙布韦和利巴韦林治疗24周而非12周时，SVR12率更高（94.2%对88.6%）。不良事件通常较轻，最常见的包括疲劳、头痛、恶心和腹泻。
由奥比他韦/帕利瑞韦/利托那韦和达沙布韦组成的治疗方案在治疗HCV 1型感染方面高度有效，不良事件最少。预计它将在有很大机会治愈HCV感染的新型药物储备中发挥重要作用。
