Eisai Inc., Nutley, NJ, USA.
Syneos Health, Raleigh, NC, USA.
J Psychopharmacol. 2022 Jun;36(6):745-755. doi: 10.1177/02698811221080459.
Lemborexant is a dual orexin receptor antagonist approved to treat insomnia in adults in several countries including the USA, Canada, and Japan.
This study was conducted to investigate effects of lemborexant and alcohol coadministration on postural stability, cognitive performance, and the pharmacokinetics, safety, and tolerability of lemborexant.
This was a Phase 1, double-blind, placebo-controlled, four-period crossover study in 32 healthy adults. Individuals were randomized into one of four treatment sequences to receive single doses of placebo, lemborexant 10 mg (LEM10), alcohol (males, 0.7 g/kg; females, 0.6 g/kg), and LEM10 plus alcohol, each separated by a 14-day washout. Postural stability (body sway) was measured by ataxiameter and a cognitive performance assessment battery evaluated four domains of attention and memory.
Pharmacodynamic outcomes were analyzed for the 18 participants who completed all four treatments. Change from baseline in body sway showed no significant differences between lemborexant plus alcohol versus alcohol alone. Compared with alcohol alone, coadministration of lemborexant with alcohol showed additive negative effects on cognitive performance domains, corresponding approximately with peak plasma lemborexant concentrations (median = 1.5 h). Cognitive performance was also impaired with lemborexant alone at 0.5 and 2 h in this experimental paradigm with morning dosing. Alcohol increased plasma lemborexant exposure by 70% based on area under the curve to 72 h, and increased peak plasma lemborexant concentrations by 35%. The most commonly reported treatment-emergent adverse event was somnolence.
Coadministration of lemborexant with alcohol showed additive negative effects on cognitive measures, but not on postural stability, compared with alcohol alone. Lemborexant exposure was increased with alcohol. Lemborexant alone or with alcohol was well tolerated. Patients are advised not to consume alcohol with lemborexant.
仑美昔布是一种双重食欲素受体拮抗剂，已在包括美国、加拿大和日本在内的多个国家获得批准，用于治疗成年人失眠症。
本研究旨在考察仑美昔布与酒精联合应用对姿势稳定性、认知功能以及仑美昔布的药代动力学、安全性和耐受性的影响。
这是一项在 32 名健康成年人中进行的 1 期、双盲、安慰剂对照、4 周期交叉研究。个体随机分为 4 种治疗序列中的 1 种，分别接受单次安慰剂、仑美昔布 10mg（LEM10）、酒精（男性 0.7g/kg；女性 0.6g/kg）和 LEM10 加酒精，每种药物治疗之间间隔 14 天洗脱期。通过晃动测量仪测量姿势稳定性（身体晃动），并使用认知性能评估工具包评估注意力和记忆的四个领域的认知功能。
对完成所有 4 种治疗的 18 名参与者进行了药效学结局分析。与单独使用酒精相比，仑美昔布加酒精组的身体晃动自基线的变化无显著差异。与单独使用酒精相比，仑美昔布与酒精联合使用对认知功能域表现出相加的负面影响，这与仑美昔布的峰值血浆浓度（中位数=1.5 小时）大致相符。在该实验方案中，仑美昔布单独使用时，在早晨给药后 0.5 和 2 小时，认知功能也受到损害。酒精使仑美昔布的 AUC0-72h 增加了 70%，使峰值血浆仑美昔布浓度增加了 35%。最常报告的治疗相关不良事件是嗜睡。
与单独使用酒精相比，仑美昔布与酒精联合使用对认知测量指标有相加的负面影响，但对姿势稳定性无影响。仑美昔布的暴露量随着酒精的增加而增加。仑美昔布单独或联合使用具有良好的耐受性。建议患者不要将仑美昔布与酒精同时使用。
