Kakuda Thomas N, Leopold Lorant, Nijs Steven, Vandevoorde Ann, Crauwels Herta M, Bertelsen Kirk M, Stevens Marita, Witek James, van Delft Yvon, Tomaka Frank, Hoetelmans Richard M W
Janssen Research and Development, LLC, Titusville, NJ, USA.
Janssen Infectious Diseases BVBA, Beerse, Belgium.
J Clin Pharmacol. 2014 May;54(5):563-73. doi: 10.1002/jcph.245.
Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) may require treatment with an HIV non-nucleoside reverse transcriptase inhibitor (NNRTI), for example, rilpivirine or etravirine, and an HCV direct-acting antiviral drug such as telaprevir. In a two-panel, two-way, crossover study, healthy volunteers were randomized to receive etravirine 200 mg twice daily ± telaprevir 750 mg every 8 hours or rilpivirine 25 mg once daily ± telaprevir 750 mg every 8 hours. Pharmacokinetic assessments were conducted for each drug at steady-state when given alone and when coadministered; statistical analyses were least-square means with 90% confidence intervals. Telaprevir minimum plasma concentration (Cmin), maximum plasma concentration (Cmax), and area under the concentration-time curve (AUC) decreased 25%, 10%, and 16%, respectively, when coadministered with etravirine and 11%, 3%, and 5%, respectively, when coadministered with rilpivirine. Telaprevir did not affect etravirine pharmacokinetics, but increased rilpivirine Cmin, Cmax, and AUC by 93%, 49%, and 78%, respectively. Both combinations were generally well tolerated. The small decrease in telaprevir exposure when coadministered with etravirine is unlikely to be clinically relevant. The interaction between telaprevir and rilpivirine is not likely to be clinically relevant under most circumstances. No dose adjustments are deemed necessary when they are coadministered.
人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）合并感染可能需要使用HIV非核苷类逆转录酶抑制剂（NNRTI）进行治疗，例如利匹韦林或依曲韦林，以及一种HCV直接抗病毒药物，如特拉匹韦。在一项双组、双向、交叉研究中，健康志愿者被随机分组，分别接受依曲韦林200毫克每日两次±特拉匹韦750毫克每8小时一次，或利匹韦林25毫克每日一次±特拉匹韦750毫克每8小时一次。在单独给药和联合给药的稳态时对每种药物进行药代动力学评估；统计分析采用90%置信区间的最小二乘均值。与依曲韦林合用时，特拉匹韦的最低血浆浓度（Cmin）、最高血浆浓度（Cmax）和浓度-时间曲线下面积（AUC）分别下降25%、10%和16%，与利匹韦林合用时分别下降11%、3%和5%。特拉匹韦不影响依曲韦林的药代动力学，但使利匹韦林的Cmin、Cmax和AUC分别增加93%、49%和78%。两种组合总体耐受性良好。与依曲韦林合用时特拉匹韦暴露量的小幅下降在临床上不太可能具有相关性。在大多数情况下，特拉匹韦与利匹韦林之间的相互作用在临床上不太可能具有相关性。联合给药时无需调整剂量。
