Barzaghi N, Gatti G, Manni R, Galimberti C A, Zucca C, Tartara A, Perucca E
Department of Internal Medicine, University of Pavia, Italy.
Ther Drug Monit. 1989 Nov;11(6):661-6. doi: 10.1097/00007691-198911000-00009.
The relationship between the serum concentration of phenobarbital and its pharmacodynamic effects was assessed in a double-blind controlled study in eight normal volunteers who were given single oral doses of phenobarbital (200 mg) and placebo according to a randomized cross-over design. Compared with the placebo session, phenobarbital was found to induced CNS-depressing effects as assessed by visual analogue rating scales (VARS) and critical flicker fusion tests (CFF), whereas no significant effects were detected on choice reaction times, tappings, and digit symbol substitutions. There was a clear-cut dissociation between the time course of serum phenobarbital levels, which remained at a plateau throughout most of the period of observation (up to 72 h) and its subjective (VARS) and objective (CFF) effects, which could be documented only for up to 9 h after administration. These data suggest that pharmacodynamic tolerance develops rapidly even after a single oral dose of the drug. Multiple Sleep Latency Tests (MSLTs) were also performed in the same subjects and showed that phenobarbital increases diurnal drowsiness and attenuates the circadian variation in drowsy state that is seen under control conditions. MLSTs appeared to be superior to other tests in documenting the sedative effects of the barbiturate.
在一项双盲对照研究中，对8名正常志愿者进行了评估，这些志愿者按照随机交叉设计，单次口服苯巴比妥（200毫克）和安慰剂。与服用安慰剂阶段相比，通过视觉模拟评分量表（VARS）和临界闪烁融合测试（CFF）评估发现，苯巴比妥可产生中枢神经系统抑制作用，而在选择反应时间、敲击和数字符号替换方面未检测到显著影响。血清苯巴比妥水平在大部分观察期（长达72小时）内保持在平台期，其主观（VARS）和客观（CFF）效应在给药后仅9小时内可记录到，二者之间存在明显的分离。这些数据表明，即使单次口服该药物后，药效学耐受性也会迅速发展。还对同一受试者进行了多次睡眠潜伏期测试（MSLT），结果显示苯巴比妥会增加日间嗜睡，并减弱在对照条件下观察到的困倦状态的昼夜变化。在记录巴比妥类药物的镇静作用方面，MSLT似乎优于其他测试。
