Merck Sharp - Dohme Corp., Whitehouse Station, NJ, USA.
Sleep. 2013 Feb 1;36(2):259-67. doi: 10.5665/sleep.2386.
Suvorexant (MK-4305) is an orexin receptor antagonist being developed for the treatment of insomnia. This report describes the effects of nighttime administration of suvorexant on polysomnography (PSG) sleep parameters in healthy young men.
Randomized, double-blind, placebo-controlled, 4-period crossover PSG study, followed by an additional 5(th) period to assess pharmacokinetics.
Sleep laboratory.
Healthy young men between 18 and 45 years of age (22 enrolled, 19 completed).
Periods 1-4: suvorexant (10 mg, 50 mg, or 100 mg) or placebo 1 h before nighttime PSG recording. Period 5: suvorexant 10 mg, 50 mg, or 100 mg.
In Periods 1-4, overnight sleep parameters were recorded by PSG and next-morning residual effects were assessed by psychomotor performance tests and subjective assessments. Statistically significant sleep-promoting effects were observed with all doses of suvorexant compared to placebo. Suvorexant 50 mg and 100 mg significantly decreased latency to persistent sleep and wake after sleep onset time, and increased sleep efficiency. Suvorexant 10 mg significantly decreased wake after sleep onset time. There were no statistically significant effects of suvorexant on EEG frequency bands including delta (slow wave) activity based on power spectral analysis. Suvorexant was well tolerated. There was no evidence of next-day residual effects for suvorexant 10 mg. Suvorexant 50 mg statistically significantly reduced subjective alertness, and suvorexant 100 mg significantly increased reaction time and reduced subjective alertness. There were no statistically significant effects of any suvorexant dose on digit symbol substitution test performance. In Period 5, plasma samples of suvorexant were collected for pharmacokinetic evaluation. The median T(max) was 3 hours and apparent terminal t(½) was 9-13 hours.
In healthy young men without sleep disorders, suvorexant promoted sleep with some evidence of residual effects at the highest doses.
苏沃雷生（MK-4305）是一种食欲素受体拮抗剂，正在开发用于治疗失眠症。本报告描述了在健康年轻男性中，夜间给予苏沃雷生对多导睡眠图（PSG）睡眠参数的影响。
随机、双盲、安慰剂对照、4 期交叉 PSG 研究，随后进行第 5 期以评估药代动力学。
睡眠实验室。
年龄在 18 至 45 岁之间的健康年轻男性（22 名入组，19 名完成）。
第 1-4 期：苏沃雷生（10 毫克、50 毫克或 100 毫克）或安慰剂在夜间 PSG 记录前 1 小时给药。第 5 期：苏沃雷生 10 毫克、50 毫克或 100 毫克。
在第 1-4 期，通过 PSG 记录整夜睡眠参数，并通过精神运动性能测试和主观评估评估次日清晨的残留效应。与安慰剂相比，所有剂量的苏沃雷生均观察到显著的促眠作用。苏沃雷生 50 毫克和 100 毫克显著降低了入睡潜伏期和睡眠后觉醒时间，增加了睡眠效率。苏沃雷生 10 毫克显著降低了睡眠后觉醒时间。基于功率谱分析，苏沃雷生对脑电图频带（包括慢波活动）无统计学显著影响。苏沃雷生耐受性良好。苏沃雷生 10 毫克无次日残留效应证据。苏沃雷生 50 毫克显著降低了主观警觉性，苏沃雷生 100 毫克显著增加了反应时间并降低了主观警觉性。苏沃雷生任何剂量均对数字符号替代测试无统计学显著影响。在第 5 期，采集苏沃雷生的血浆样本进行药代动力学评估。中位数 T(max)为 3 小时，表观终末 t(½)为 9-13 小时。
在无睡眠障碍的健康年轻男性中，苏沃雷生可促进睡眠，最高剂量时存在一些残留效应的证据。
