Spénard J, Caillé G, de Montigny C, Vézina M, Ouellette J, Larivière L, Trudel F
Département de pharmacologie, Faculté de médecine, Université de Montréal, Québec, Canada.
Biopharm Drug Dispos. 1988 Sep-Oct;9(5):457-64. doi: 10.1002/bod.2510090504.
In a randomized crossover study, twelve patients presenting a generalized anxiety disorder received either a 1 mg oral tablet or a 1 mg sublingual tablet of lorazepam three times daily for 7 days. After a 7-day washout period, each patient received a 7-day treatment with the other tablet form. Treatments were administered in a double-blind manner using placebos of both the oral and sublingual tablets. Psychiatric evaluations were carried out before and following each of the three periods. Blood samples were drawn at intervals for 48 h following the last dose of each treatment. The plasma concentrations of lorazepam were measured by gas chromatography using an electron-capture detector. Both the oral and sublingual lorazepam produced a significant anxiolytic effect; there was no statistically significant difference between the therapeutic effectiveness of the two forms of lorazepam. The main pharmacokinetic parameters for the oral and sublingual tablets were, respectively: elimination half-life 15.6h and 11.7h; maximal concentration 40.8 ng ml-1 and 42.2 ng ml-1; time to reach maximal concentration 1.2h and 1.4h; corrected area under the curve 310.6 ng hml-1 and 313.6 ng hml-1. There was no statistically significant difference between the oral and sublingual tablets for any of the pharmacokinetic parameters measured.
在一项随机交叉研究中，12名患有广泛性焦虑症的患者每天三次分别服用1毫克劳拉西泮口服片或1毫克劳拉西泮舌下片，持续7天。经过7天的洗脱期后，每位患者接受另一种片剂形式的7天治疗。使用口服和舌下片剂的安慰剂以双盲方式给药。在三个疗程的每个疗程前后进行精神科评估。在每次治疗的最后一剂后48小时内间隔采集血样。使用电子捕获检测器通过气相色谱法测量劳拉西泮的血浆浓度。口服和舌下含服劳拉西泮均产生显著的抗焦虑作用；两种形式的劳拉西泮的治疗效果之间没有统计学上的显著差异。口服片和舌下片的主要药代动力学参数分别为：消除半衰期15.6小时和11.7小时；最大浓度40.8纳克/毫升和42.2纳克/毫升；达到最大浓度的时间1.2小时和1.4小时；曲线下校正面积310.6纳克·小时/毫升和313.6纳克·小时/毫升。所测量的任何药代动力学参数在口服片和舌下片之间均无统计学上的显著差异。
