Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo
Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo
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DOI：
10.1016/s0009-9236(98)90139-4
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发表时间：
1998-11-01
影响因子：
6.7
通讯作者：
Shader, RI
中科院分区：
文献类型：
--
作者：
Greenblatt, DJ;Harmatz, JS;Shader, RI
目的：研究扎来普隆和唑吡坦这两种结构不同的苯二氮卓类受体激动剂的剂量、血药浓度和时间与药效学的关系。方法：10名健康男性志愿者接受单剂量安慰剂、扎来普隆10 mg、扎来普隆20 mg、唑吡坦10 mg和唑吡坦20 mg的双盲交叉试验，试验间隔为48小时。结果：扎来普隆和唑吡坦在给药后8~24小时内的血药浓度与药效学无明显相关性。然而，扎来普隆的消除更快(表观消除半衰期[t(1/2)]为1小时)，表观口服清除量(约4300毫升/分钟)高于唑吡坦(t(1/2)，2.0~2.2小时；表观口服清除量(340~380毫升/分钟))。主动治疗产生了与苯二氮卓类激动剂活性一致的药效学效应：自我和观察者评级的镇静，数字符号替代试验(DSST)操作的损害，记忆力受损，以及β频率范围内脑电活动的增加。激动剂的总体效力顺序如下：安慰剂；10毫克扎来普隆；20毫克扎莱普隆；10毫克唑吡坦；20毫克唑吡坦；在一些指标上，20毫克扎来普隆与10毫克唑吡坦相当。唑吡坦20 mg的量化效应远远超过其他处理。结论：扎来普隆和唑吡坦的苯二氮卓类激动剂效应具有剂量和浓度依赖性。在通常的临床有效催眠剂量(两种药物均为10毫克)下，唑吡坦的兴奋作用超过扎来普隆。
Purpose: This study evaluated the relationship of dose, plasma concentration, and time to the pharmacodynamics of zaleplon and zolpidem, 2 structurally distinct benzodiazepine receptor agonists.Method: Ten healthy male volunteers received single oral doses of placebo, 10 mg zaleplon, 20 mg zaleplon, 10 mg zolpidem, and 20 mg zolpidem in a double-blind, 5-condition crossover study, with 48 hours elapsing between trials. Plasma drug concentrations and pharmacodynamic effects were measured during the 8 to 24 hours after administration.Results: Kinetics of zaleplon and zolpidem were not significantly related to dose. However, zaleplon had more rapid elimination (apparent elimination half-life [t(1/2)] of I hour) and higher apparent oral clearance (approximately 4300 mL/min) than zolpidem (t(1/2), 2.0 to 2.2 hours; apparent oral clearance, 340 to 380 mL/min). Active treatments produced pharmacodynamic effects consistent with benzodiazepine agonist activity: self- and observer-rated sedation, impairment of digit symbol substitution test (DSST) performance, impaired memory, and increased electroencephalographic activity in the beta frequency range. The overall order of agonist potency was as follows: placebo < 10 mg zaleplon < 20 mg zaleplon < 10 mg zolpidem < 20 mg zolpidem; on a number of measures, 20 mg zaleplon was comparable to 10 mg zolpidem. Quantitative effects of zolpidem 20 mg far exceeded those of other treatments. Dynamic effects of both drugs were significantly related to plasma concentration.Conclusions: Benzodiazepine agonist effects of zaleplon and zolpidem were dose and concentration dependent. At the usual clinically effective hypnotic dose (10 mg of either drug), agonist effects of zolpidem exceeded those of zaleplon.