Mattila M J, Aranko K, Mattila M E, Strömberg C
Eur J Clin Pharmacol. 1984;26(3):375-80. doi: 10.1007/BF00548770.
Fourteen, healthy students volunteered for a double-blind, cross-over trial of temazepam 20 mg (soft gelatine capsule), nitrazepam 10 mg (uncoated tablet) and placebo in matched formulations, single doses of each being given for 10 nights with a three-week wash-out period between each treatment. Residual drug effects were measured objectively (psychomotor skills) and subjectively (visual analogue scales) in the morning and afternoon of Days 0 (before the first tablet), 1 and 10. The subjects also recorded various events during each treatment period. Serum benzodiazepine concentrations were bioassayed in blood samples taken after the last assessment. Both benzodiazepines shortened sleep latency during the first few nights, and nitrazepam prolonged the duration of sleep. The residual effect of drowsiness was noted during the nitrazepam period, whilst temazepam proved less sedating. The 'morning after' effect was a subjective observation and not an objective measurement. The learning effect interfered with the complex objective assessments, and simple measurement of exophoria with the Maddox wing test provided the clearest objective evidence of drug effects. On Day 10 residual concentrations of nitrazepam were detectable in the serum whereas the level of temazepam was found to be low or negligible. It is concluded, that temazepam 20 mg in a soft gelatine capsule is a suitable hypnotic for subjects whose daily work requires constant alertness.
14名健康学生自愿参加一项双盲交叉试验,试验药物为20毫克替马西泮(软胶囊)、10毫克硝西泮(无包衣片)以及与之匹配的安慰剂制剂,每种药物单剂量给药,连续服用10个晚上,每次治疗之间间隔3周的洗脱期。在第0天(服用第一片药之前)、第1天和第10天的上午和下午,客观(心理运动技能)和主观(视觉模拟量表)测量残留药物效应。受试者还记录了每个治疗期间的各种事件。在最后一次评估后采集的血样中对血清苯二氮䓬浓度进行生物测定。两种苯二氮䓬类药物在前几个晚上均缩短了睡眠潜伏期,硝西泮延长了睡眠时间。在硝西泮治疗期间注意到有嗜睡的残留效应,而替马西泮的镇静作用较小。“宿醉”效应是一种主观观察而非客观测量。学习效应干扰了复杂的客观评估,使用马多克斯翼试验简单测量外隐斜提供了最清晰的药物效应客观证据。在第10天,血清中可检测到硝西泮的残留浓度,而替马西泮的水平较低或可忽略不计。得出的结论是,20毫克软胶囊装的替马西泮对于日常工作需要持续警觉的受试者是一种合适的催眠药。