Shader R I, Pary R J, Harmatz J S, Allison S, Locniskar A, Greenblatt D J
J Clin Psychiatry. 1984 Oct;45(10):411-3.
In a double-blind parallel-group pharmacokinetic and pharmacodynamic study, 31 healthy volunteers received single oral doses of prazepam (10 mg), clorazepate (7.5 mg), or diazepam (5 mg). Appearance in plasma of diazepam and of desmethyldiazepam was rapid after administration of diazepam and clorazepate, respectively, with peak plasma concentrations reached within an average of 1 hour. After oral prazepam, however, desmethyldiazepam appeared in blood slowly, with the highest mean concentration at 6 hours postdosage. Clinical self-ratings of fatigue and of "feeling spacey" were significantly different among groups, with changes over baseline being more marked with clorazepate and diazepam than with prazepam. Thus, differences in absorption rate of orally administered benzodiazepines can lead to differences in the intensity of single-dose effects, despite administration of doses that are equivalent in terms of long-term anxiolytic efficacy.
在一项双盲平行组药代动力学和药效学研究中，31名健康志愿者分别单次口服10毫克普拉西泮、7.5毫克氯氮卓或5毫克地西泮。服用地西泮和氯氮卓后，地西泮和去甲基地西泮分别迅速出现在血浆中，平均1小时内达到血浆峰值浓度。然而，口服普拉西泮后，去甲基地西泮在血液中出现得较慢，给药后6小时达到最高平均浓度。各组之间疲劳和“感觉迷糊”的临床自我评分存在显著差异，氯氮卓和地西泮组相对于基线的变化比普拉西泮组更明显。因此，尽管口服苯二氮䓬类药物的剂量在长期抗焦虑疗效方面相当，但吸收速率的差异会导致单剂量效应强度的差异。
