Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir
Drug-drug interaction profile of the all-oral anti-hepatitis C virus regimen of paritaprevir/ritonavir, ombitasvir, and dasabuvir
复制标题
DOI：
10.1016/j.jhep.2015.01.026
复制
发表时间：
2015-07-01
影响因子：
25.7
通讯作者：
Dutta, Sandeep
中科院分区：
文献类型：
--
作者：
Menon, Rajeev M.;Badri, Prajakta S.;Dutta, Sandeep
背景与目的：Paritapvir(与利托那韦合用，PTV/r)、奥比沙韦(OBV)和达沙布韦(Dasabuvir，DSV)是治疗慢性丙型肝炎病毒感染的直接作用抗病毒药物。共进行了13项研究，以描述OBV、PTV/r和DSV 3D方案与不同药物在健康志愿者中的相互作用，为丙型肝炎病毒感染患者提供给药建议。方法：评价吉非罗齐、酮康唑、卡马西平、华法林、奥美拉唑、地高辛、普伐他汀和瑞舒伐他汀的药物相互作用机制。对氨氯地平、速尿、阿普唑仑、唑吡坦、度洛西汀、艾司匹兰、美沙酮、丁丙诺啡/纳洛酮和口服避孕药与丙型肝炎病毒感染者常用药物的药物相互作用进行了评估。结果：OBV方案、PTV/r方案和DSV方案联合给药，均可获得较高的血药浓度和最大血药浓度。
Background & Aims: Paritaprevir (administered with ritonavir, PTV/r), ombitasvir (OBV), and dasabuvir (DSV) are direct-acting antiviral agents (DAAs) for the treatment of chronic hepatitis C virus (HCV) infection. Thirteen studies were conducted to characterize drug-drug interactions for the 3D regimen of OBV, PTV/r, and DSV and various medications in healthy volunteers to inform dosing recommendations in HCV-infected patients.Methods: Mechanism-based drug-drug interactions were evaluated for gemfibrozil, ketoconazole, carbamazepine, warfarin, omeprazole, digoxin, pravastatin, and rosuvastatin. Drug-drug interactions with medications commonly used in HCV-infected patients were evaluated for amlodipine, furosemide, alprazolam, zolpidem, duloxetine, escitalopram, methadone, buprenorphine/naloxone, and oral contraceptives. Ratios of geometric means with 90% confidence intervals for maximum plasma concentration (C-max) and area under the plasma concentration-time curve (AUC) were used to determine the magnitude of interaction.Results: Coadministration with the 3D regimen of OBV, PTV/r, and DSV resulted in a