Ochs H R, Greenblatt D J, Lüttkenhorst M, Verburg-Ochs B
Eur J Clin Pharmacol. 1984;26(4):499-503. doi: 10.1007/BF00542148.
Sixteen healthy volunteers, aged 19 to 62 years, took a single 20-mg oral dose of clobazam and the serum concentrations of clobazam and desmethylclobazam were measured for the following 7 days. The mean kinetic variables for clobazam were: volume of distribution 1.31/kg, elimination half-life 24h, total clearance 0.47 ml/min/kg. 13 of the volunteers then took clobazam 5 mg twice daily for 22 consecutive days. Serum concentrations were measured during and after this period. Both clobazam and desmethylclobazam showed slow and extensive accumulation, their steady-state kinetics being entirely consistent with those observed after single doses. Elimination of both compounds after termination of treatment was equally slow. Clinical self-rating of morning sedation indicated a significant increase over baseline in subjective perception of sedation during the treatment period, and this effect persisted into the washout period. However, sedation did not increase in parallel with accumulating levels of clobazam and desmethylclobazam, probably due to functional adaptation or tolerance.
16名年龄在19至62岁之间的健康志愿者口服了20毫克单剂量的氯巴占，并在接下来的7天内测量了氯巴占和去甲基氯巴占的血清浓度。氯巴占的平均动力学变量为：分布容积1.31升/千克，消除半衰期24小时，总清除率0.47毫升/分钟/千克。然后，13名志愿者连续22天每天两次服用5毫克氯巴占。在此期间及之后测量血清浓度。氯巴占和去甲基氯巴占均显示出缓慢而广泛的蓄积，其稳态动力学与单次给药后观察到的完全一致。治疗终止后两种化合物的消除同样缓慢。早晨镇静的临床自评表明，治疗期间镇静的主观感受较基线有显著增加，且这种效应持续到洗脱期。然而，镇静作用并未与氯巴占和去甲基氯巴占的蓄积水平平行增加，这可能是由于功能适应或耐受性所致。
