The Johns Hopkins Hospital, Baltimore, MD, USA.
Am J Health Syst Pharm. 2011 Nov 1;68(21):2049-54. doi: 10.2146/ajhp110083.
The pharmacokinetic interaction of etravirine and raltegravir is reviewed, with discussion of implications for clinical practice.
Etravirine (a second-generation nonnucleoside reverse transcriptase inhibitor) and raltegravir (an integrase strand- transfer inhibitor) are two agents approved by the Federal Food and Drug Administration for use in human immunodeficiency virus (HIV) treatment-resistant patients. Minimal data exist on the concurrent use of raltegravir with etravirine. This combination would offer treatment-experienced HIV patients a novel pharmacotherapy plan including two new fully active agents. Etravirine induces uridine diphosphate- glucuronosyltransferase 1A1 and reduces the raltegravir minimum concentration (C(min)) by 34% when administered concurrently in healthy volunteers. In a case series of four HIV treatment-resistant patients initiated on an antiretroviral regimen including standard doses of etravirine and raltegravir, poor virological control was demonstrated. Two of these four patients had a raltegravir C(min) below the 95% minimum inhibitory concentration. In a larger study (n = 103), sustained virological control (viral loads of <50 copies/mL) resulted when HIV treatment-resistant patients received standard doses of darunavir, ritonavir, etravirine, raltegravir, and nucleoside analogs with or without enfuvirtide. Debate exists regarding the best raltegravir pharmacokinetic parameter to evaluate (C(min) or the area under the concentration curve/50% effective concentration). Recent data in HIV treatment-naive patients support a negative association between a low raltegravir C(min) (≤43 ng/mL) and virological suppression.
The need to adjust the dosage of raltegravir in HIV-infected patients who are also receiving etravirine is unclear. In such patients who have an extensive history of HIV disease treatment, prescribing raltegravir 1200 mg/day, rather than the standard 800 mg/day, may be prudent to prevent the development of treatment-resistant virus and to achieve an optimal virological response.
本文回顾了依曲韦林与雷特格韦的药代动力学相互作用，并讨论了其对临床实践的意义。
依曲韦林（第二代非核苷类逆转录酶抑制剂）和雷特格韦（整合酶链转移抑制剂）是两种经美国食品和药物管理局批准用于治疗人类免疫缺陷病毒（HIV）耐药患者的药物。目前仅有少量关于雷特格韦与依曲韦林同时使用的数据。对于治疗经验丰富的 HIV 患者而言，这种联合用药方案为其提供了一种新的包含两种全新有效药物的治疗方案。依曲韦林在健康志愿者中与雷特格韦同时使用时，可诱导尿苷二磷酸-葡糖醛酸基转移酶 1A1，使雷特格韦的最低浓度（Cmin）降低 34%。在包括标准剂量依曲韦林和雷特格韦的抗逆转录病毒治疗方案起始治疗的 4 例 HIV 耐药患者的病例系列研究中，显示出较差的病毒学控制效果。其中 2 例患者的雷特格韦 Cmin 低于 95%最小抑菌浓度。在一项更大的研究（n=103）中，当 HIV 耐药患者接受标准剂量的达芦那韦、利托那韦、依曲韦林、雷特格韦和核苷类似物联合或不联合恩夫韦肽治疗时，病毒学控制得到持续维持（病毒载量<50 拷贝/mL）。目前对于评估最佳的雷特格韦药代动力学参数（Cmin 或浓度曲线下面积/50%有效浓度）存在争议。最近在 HIV 初治患者中的数据支持低雷特格韦 Cmin（≤43ng/mL）与病毒学抑制之间存在负相关。
尚不清楚接受依曲韦林治疗的 HIV 感染患者是否需要调整雷特格韦的剂量。在有大量 HIV 疾病治疗史的此类患者中，为了防止耐药病毒的产生并获得最佳的病毒学应答，谨慎起见，可将雷特格韦的剂量调整为 1200mg/天，而非标准剂量 800mg/天。
