Boulenger J P, Smokcum R, Lader M
J Clin Psychopharmacol. 1984 Feb;4(1):25-31.
This study was designed to investigate the relationship between subjective and objective effects of a benzodiazepine on the one hand, and the rate of increase of plasma concentration on the other. The pharmacokinetic variables of 10 normal volunteers were calculated following a single intravenous bolus injection of 1 mg of lorazepam, a benzodiazepine devoid of active metabolites. In six of the subjects rates of infusion could be calculated in order to achieve the same plasma concentration after 1 hour and 2 hours. In the main study, lorazepam was infused at two different rates on two separate occasions, with a third placebo infusion occasion. A balanced crossover design was used with single-blind procedures. Plasma concentrations, subjective ratings, quantified EEG recordings, and psychological performance tests were estimated before and at 1, 2, and 3 hours after the start of the infusions. The peak plasma concentrations achieved were the same at the end of the two drug infusions. EEG and some performance tests paralleled the plasma concentrations fairly closely, but subjective effects did not reach their maximum until the 3-hour point and were significantly greater after the 2-hour than after the 1-hour infusion. Drug doses, rate of penetration into the brain, and duration of exposure to the increasing concentrations of lorazepam seem more relevant factors for the time course and the intensity of the various initial effects of the drug than the rate of increase of plasma levels.
本研究旨在一方面探究苯二氮䓬的主观和客观效应之间的关系，另一方面探究血浆浓度的上升速率之间的关系。在10名正常志愿者单次静脉推注1毫克劳拉西泮（一种无活性代谢物的苯二氮䓬）后，计算其药代动力学变量。在其中6名受试者中，可以计算输注速率，以便在1小时和2小时后达到相同的血浆浓度。在主要研究中，劳拉西泮在两个不同的场合以两种不同的速率输注，还有第三次输注安慰剂的场合。采用平衡交叉设计和单盲程序。在输注开始前以及输注开始后1小时、2小时和3小时评估血浆浓度、主观评分、定量脑电图记录和心理性能测试。在两次药物输注结束时达到的血浆峰值浓度相同。脑电图和一些性能测试与血浆浓度相当密切地平行，但主观效应直到3小时时才达到最大值，并且在2小时输注后比1小时输注后显著更大。药物剂量、进入大脑的渗透速率以及暴露于不断增加的劳拉西泮浓度的持续时间，似乎比血浆水平的上升速率对于药物各种初始效应的时间进程和强度更具相关因素。
