直接作用抗丙型肝炎病毒药物：临床药理学与未来方向。
Direct Acting Anti-hepatitis C Virus Drugs: Clinical Pharmacology and Future Direction.
作者信息
Geddawy Ayman, Ibrahim Yasmine F, Elbahie Nabil M, Ibrahim Mohammad A
机构信息
Department of Pharmacology, Faculty of Medicine, Minia University, El- Minia 61519, Egypt.
Department of Pharmacology, Faculty of Medicine, Alexandria UniversityEgypt.
出版信息
J Transl Int Med. 2017 Mar 31;5(1):8-17. doi: 10.1515/jtim-2017-0007. eCollection 2017 Mar.
Abstract
Chronic hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The introduction of direct acting antiviral agents (DAAs) for its treatment represents a major advance in terms of sustained virologic response (SVR) rates and adverse effect profiles. Mechanistically, DAAs inhibit specific HCV non-structural proteins (NS) that are vital for its replication. Boceprevir, telaprevir, simeprevir, asunaprevir, grazoprevir and paritaprevir are NS3/4A inhibitors. Ombitasvir, ledipasvir, daclatasvir, elbasvir and velpatasvir are NS5A inhibitors. Sofosbuvir and dasabuvir are NS5B inhibitors. Currently, a combination of two or more DAAs is the corner stone for the treatment of HCV infection. However, the success of DAA therapy is facing several challenges, including the potential of drug-drug interactions and resistant variance. Moreover, the shortage of relevant clinical pharmacological data and drug interaction regarding DAA is a clinical concern. The present review discusses the clinical pharmacology of DAAs with special emphasis on drug-drug interaction.
摘要
慢性丙型肝炎病毒（HCV）感染是慢性肝病的主要病因。直接作用抗病毒药物（DAA）用于其治疗，在持续病毒学应答（SVR）率和不良反应方面取得了重大进展。从机制上讲，DAA抑制对HCV复制至关重要的特定非结构蛋白（NS）。博赛匹韦、特拉匹韦、西米普明、阿舒瑞韦、格拉瑞韦和帕利瑞韦是NS3/4A抑制剂。奥比他韦、来迪帕司韦、达卡他韦、艾尔巴韦和维帕他韦是NS5A抑制剂。索磷布韦和达沙布韦是NS5B抑制剂。目前，两种或更多种DAA联合使用是治疗HCV感染的基石。然而，DAA治疗的成功面临若干挑战，包括药物相互作用和耐药变异的可能性。此外，关于DAA的相关临床药理学数据和药物相互作用的短缺是一个临床问题。本综述讨论了DAA的临床药理学，特别强调了药物相互作用。
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