Merck & Co., Inc., Whitehouse Station, NJ, USA.
J Clin Pharmacol. 2010 Dec;50(12):1461-6. doi: 10.1177/0091270009360981. Epub 2010 Feb 19.
A randomized, placebo-controlled, 2-period crossover study in subjects on methadone maintenance therapy was conducted to assess the effect of the HIV-1 integrase inhibitor, raltegravir, on the pharmacokinetics of methadone. Twelve HIV-negative male and female subjects stabilized on an oral methadone program were enrolled. Subjects maintained their prescribed oral doses of methadone throughout the study and, in each of 2 periods, received either 400 mg of raltegravir or matching placebo every 12 hours on days 1 through 10 of each treatment period with a washout of 7 days between periods. Plasma samples for analysis of methadone pharmacokinetics were collected over 24 hours postdose on day 10 of each treatment period. Safety and tolerability were assessed throughout the study. The geometric mean ratio (90% confidence interval) for methadone when administered with raltegravir relative to methadone alone was 1.00 (0.93-1.09) for area under the methadone concentration time curve from time 0 to 24 hours and 1.00 (0.94-1.07) for maximal concentration. There were no serious clinical or laboratory adverse experiences. There were no discontinuations due to an adverse experience. Coadministration of raltegravir and methadone is generally well tolerated. Raltegravir has no clinically meaningful effect on methadone pharmacokinetics. No dose adjustment is required for methadone when coadministered with raltegravir.
一项纳入接受美沙酮维持治疗的受试者、采用随机、安慰剂对照、双周期交叉设计的研究，旨在评估 HIV-1 整合酶抑制剂拉替拉韦对美沙酮药代动力学的影响。该研究纳入了 12 名 HIV 阴性的男性和女性受试者，这些受试者接受口服美沙酮方案治疗且病情稳定。在整个研究期间，受试者均维持其既定的口服美沙酮剂量，在每个治疗周期的第 1 至 10 天，每日接受 400mg 拉替拉韦或匹配安慰剂，12 小时 1 次，每个治疗周期之间洗脱期为 7 天。在每个治疗周期的第 10 天，于给药后 24 小时内采集用于分析美沙酮药代动力学的血浆样本。在整个研究过程中，评估安全性和耐受性。当与拉替拉韦联合给药时，美沙酮的几何均数比值（90%置信区间）在 0 至 24 小时的美沙酮浓度-时间曲线下面积和最大浓度方面分别为 1.00（0.93-1.09）和 1.00（0.94-1.07）。没有出现严重的临床或实验室不良事件。没有因不良事件而停药。拉替拉韦与美沙酮联合使用通常具有良好的耐受性。拉替拉韦对美沙酮的药代动力学无临床意义的影响。与拉替拉韦联合使用时，无需调整美沙酮的剂量。
