Kotegawa Tsutomu, Tsutsumi Kimiko, Imai Hiromitsu, Ohashi Kyoichi, Nakano Shigeyuki
Int J Clin Pharmacol Ther. 2014 Jun;52(6):519-24. doi: 10.5414/CP202084.
The aim of this study was to evaluate the effect of sleep disturbance on the pharmacokinetics, especially on the absorption, of lorazepam in humans. Eight healthy male volunteers received a single oral dose of lorazepam 1 mg before sleep on two occasions in a cross-over design. In either of the two doses, subjects were intermittently exposed to noise for 1.5 hours after oral lorazepam administration. Plasma lorazepam concentrations were measured by HPLC. The exposure to noise significantly prolonged tmax (control vs. noise: 2.0 vs. 3.0 hours) and significantly decreased AUC of lorazepam in the absorption phase. The reduction was 54% (95% CI, 15 - 75%) and 24% (3 - 40%) for AUC (0 - 1 hours) and AUC (0 - 3 hours), respectively. No significant changes were observed in other pharmacokinetic parameters. The results of this study suggest that the onset of drug action after oral lorazepam administration can be altered by sleep disturbance.
本研究的目的是评估睡眠障碍对劳拉西泮在人体药代动力学方面的影响，尤其是对其吸收的影响。八名健康男性志愿者采用交叉设计，在两个不同时间段于睡前单次口服1毫克劳拉西泮。在两次给药中的任何一次，口服劳拉西泮后，受试者会间歇性暴露于噪音环境中1.5小时。采用高效液相色谱法测定血浆劳拉西泮浓度。暴露于噪音环境显著延长了达峰时间（对照组与噪音组：2.0小时对3.0小时），并显著降低了吸收相劳拉西泮的药时曲线下面积。药时曲线下面积（0 - 1小时）和药时曲线下面积（0 - 3小时）的降低幅度分别为54%（95%置信区间，15 - 75%）和24%（3 - 40%）。其他药代动力学参数未观察到显著变化。本研究结果表明，口服劳拉西泮后的药物起效时间可因睡眠障碍而改变。
