Brayer Samuel W, Reddy K Rajender
University of Pennsylvania, 2 Dulles, 3400 Spruce Street, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
Expert Rev Gastroenterol Hepatol. 2015 May;9(5):547-58. doi: 10.1586/17474124.2015.1032938. Epub 2015 Apr 6.
Chronic hepatitis C virus (HCV) infection is a worldwide health issue. All oral therapies are quickly replacing peg-interferon-based treatment regimens. Developing effective, well tolerated, treatments accessible for difficult to treat populations remains an unmet need. Ritonavir, an HIV-1 protease inhibitor, has pharmacokinetic properties that enhance the activity of concomitantly administered direct acting antivirals against HCV. Ritonavir inhibits Cytochrome P450 isozyme 3A4, diminishing first pass effect and hepatic metabolism, changing the pharmacokinetic parameters of Cytochrome P450 isozyme 3A4 substrates. When combined with the HCV protease inhibitor paritaprevir, ritonavir increases mean area under the curve, allowing once daily dosing. While Phase II and III clinical trials with ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir demonstrated high efficacy in those with HCV infection, drug-drug interactions warrant cautious use of ritonavir in specific patient populations. Consideration of the patients' full medication list is imperative due to the ubiquitous nature of the Cytochrome P450 isozyme 3A4 system.
慢性丙型肝炎病毒（HCV）感染是一个全球性的健康问题。所有口服疗法正在迅速取代基于聚乙二醇干扰素的治疗方案。开发有效、耐受性良好且可供难以治疗的人群使用的治疗方法仍然是未满足的需求。利托那韦是一种HIV-1蛋白酶抑制剂，具有增强同时给予的直接作用抗病毒药物对HCV活性的药代动力学特性。利托那韦抑制细胞色素P450同工酶3A4，减少首过效应和肝脏代谢，改变细胞色素P450同工酶3A4底物的药代动力学参数。当与HCV蛋白酶抑制剂帕利哌韦联合使用时，利托那韦增加曲线下平均面积，允许每日一次给药。虽然利托那韦增强的帕利哌韦、奥比他韦和达沙布韦的II期和III期临床试验在HCV感染患者中显示出高疗效，但药物相互作用需要在特定患者群体中谨慎使用利托那韦。由于细胞色素P450同工酶3A4系统的普遍性，必须考虑患者的完整用药清单。
