Mattila M J, Nurminen M L, Vainio P, Vanakoski J
Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Helsinki, Finland.
Eur J Clin Pharmacol. 1998 Jul;54(5):421-5. doi: 10.1007/s002280050486.
Caffeine counteracts various effects of traditional benzodiazepines (BZDs). As zolpidem, a short-acting hypnotic, is an atypical GABAA-BZD agonist, we investigated when caffeine would counteract the effects of zolpidem as well.
In daytime study I, zolpidem 10 mg (capsule) and caffeine 150 or 300 mg (in decaffeinated coffee) were given, alone and in combinations, to parallel groups (n = 15-17) of healthy students in double-blind and placebo-controlled manner. Objective and subjective tests were done before and 45 min and 90 min after intake. Ranked delta values (changes from baseline) were analysed by one-way contrast ANOVA and Scheffe's tests. In daytime study II, four healthy subjects took zolpidem 10 mg alone, and together with blinded caffeine 250 mg or (at -45 min) erythromycin 750 mg. Objective and subjective effects were measured and plasma zolpidem concentrations assayed at baseline and 45 min and 90 min after zolpidem intake.
In study I, practice effects after placebo (ad + 30%) were seen for letter cancellation and digit symbol substitution but not for flicker fusion tests. Zolpidem alone significantly impaired (P < 0.05 vs delta placebo) letter cancellation and digit symbol substitution at 45 min and 90 min, lowered the flicker fusion threshold at 45 min, and caused subjective drowsiness, mental slowness, clumsiness and feeling of poor performance. Caffeine alone showed a non-significant trend to improve objective performance. The combined effects of zolpidem and either dose of caffeine matched those measured after zolpidem alone. Zolpidem + caffeine 300 mg was not stronger than zolpidem + caffeine 150 mg in impairing immediate memory and causing subjective sedation. In study II, zolpidem caused objective and subjective sedation; neither caffeine nor erythromycin modulated the effects of zolpidem or plasma zolpidem concentrations.
The sedative effects of 10 mg of zolpidem are not antagonized by 150-300 mg of caffeine in pharmacodynamic or pharmacokinetic terms.
咖啡因可抵消传统苯二氮䓬类药物（BZDs）的多种效应。由于短效催眠药唑吡坦是一种非典型GABAA - BZD激动剂，我们也研究了咖啡因何时会抵消唑吡坦的效应。
在白天的研究I中，以双盲和安慰剂对照的方式，将10毫克唑吡坦（胶囊）以及150毫克或300毫克咖啡因（加入脱咖啡因咖啡中）单独及联合给予平行分组的健康学生（每组n = 15 - 17）。在服药前、服药后45分钟和90分钟进行客观和主观测试。通过单向对比方差分析和谢费检验分析排序后的差值（相对于基线的变化）。在白天的研究II中，4名健康受试者单独服用10毫克唑吡坦，以及与盲法给予的250毫克咖啡因或（在 - 45分钟时）750毫克红霉素一起服用。在基线以及唑吡坦服药后45分钟和90分钟测量客观和主观效应，并测定血浆唑吡坦浓度。
在研究I中，安慰剂组（增加30%）后在字母划消和数字符号替换测试中出现练习效应，但在闪烁融合测试中未出现。单独使用唑吡坦在45分钟和90分钟时显著损害（与安慰剂差值相比，P < 0.05）字母划消和数字符号替换，在45分钟时降低闪烁融合阈值，并引起主观嗜睡、思维迟缓、笨拙和表现不佳的感觉。单独使用咖啡因显示出改善客观表现的非显著趋势。唑吡坦与任一剂量咖啡因的联合效应与单独使用唑吡坦后测得的效应相当。在损害即时记忆和引起主观镇静方面，唑吡坦 + 300毫克咖啡因并不比唑吡坦 + 150毫克咖啡因更强。在研究II中，唑吡坦引起客观和主观镇静；咖啡因和红霉素均未调节唑吡坦的效应或血浆唑吡坦浓度。
从药效学或药代动力学角度来看，150 - 300毫克咖啡因不会拮抗10毫克唑吡坦的镇静作用。
