Thompson J Richard
J Richard Thompson, Department of Pharmacy Practice, One University Park Drive, Lipscomb University College of Pharmacy, Nashville, TN 37204, United States.
World J Gastroenterol. 2014 Jun 21;20(23):7079-88. doi: 10.3748/wjg.v20.i23.7079.
Until recently the traditional treatment for hepatitis C infection included pegylated interferon and ribavirin combination therapy. The sustained virological response (SVR) seen with this combination is poor and requires lengthy treatment to achieve. Additionally, significant side effects and numerous contraindications prevented many patients from being successfully treated with this therapy. In 2011, two new protease inhibitors, telaprevir and boceprevir, were approved for use with pegylated interferon and ribavirin in the United States by the United States Food and Drug Administration. These agents have significantly improved SVR rates; however significant problems with toxicity remain including severe skin rash and neutropenia. There are a wide range of compounds in late stage development for the future treatment of hepatitis C that exploit many different mechanisms of viral inhibition. Some of these compounds include additional protease inhibitors, like telaprevir and boceprevir, as well as inhibitors of other nonstructural proteins in the viral genome such as NS5A and NS5B, and compounds that target host proteins within the virus. Some of these agents are being developed for oral administration once daily and various combinations are being assessed for use without the need for pegylated interferon and ribavirin. This paper reviews agents in late phase development that may be commercially available within 1-2 years.
直到最近,丙型肝炎感染的传统治疗方法包括聚乙二醇化干扰素和利巴韦林联合疗法。这种联合疗法的持续病毒学应答(SVR)效果不佳,且需要长时间治疗才能实现。此外,严重的副作用和众多禁忌症使得许多患者无法通过这种疗法成功治愈。2011年,两种新型蛋白酶抑制剂特拉匹韦和波普瑞韦被美国食品药品监督管理局批准与聚乙二醇化干扰素和利巴韦林联合在美国使用。这些药物显著提高了SVR率;然而,毒性方面的重大问题仍然存在,包括严重皮疹和中性粒细胞减少。未来用于治疗丙型肝炎的处于后期开发阶段的化合物种类繁多,它们利用多种不同的病毒抑制机制。其中一些化合物包括其他蛋白酶抑制剂,如特拉匹韦和波普瑞韦,以及病毒基因组中其他非结构蛋白的抑制剂,如NS5A和NS5B,还有针对病毒内宿主蛋白的化合物。其中一些药物正被开发为每日口服一次,并且正在评估各种无需聚乙二醇化干扰素和利巴韦林的联合用药方案。本文综述了可能在1 - 2年内上市的处于后期开发阶段的药物。