Bareggi S R, Nielsen N P, Leva S, Pirola R, Zecca L, Lorini M
Int J Clin Pharmacol Res. 1986;6(4):309-14.
The kinetics of delorazepam (chlordesmethyldiazepam; CDDZ), and its major metabolite, lorazepam (LRZ) during multiple-dose therapy have been evaluated in two groups of patients with primary or secondary anxiety. The 12 patients in group 1 were 46.8 +/- less than 13.2 years while the eight in group 2 were significantly older (69.7 +/- 7.8 years). All patients were given 0.5 mg twice daily of CDDZ for 30 days. Concentrations of CDDZ and LRZ in multiple blood samples collected during the study were determined by electron-capture gas-liquid chromatography. The degree of anxiety was evaluated from the Hamilton rating scale for anxiety (HRSA). CDDZ and LRZ accumulated in plasma but the rate of accumulation of CDDZ was slower than expected from studies in young volunteers and the half-life values were significantly related to age. Steady-state levels of glucuronated LRZ were also lower in elderly patients. Data indicate that CDDZ is more slowly eliminated and less metabolized as age increases. While pre-treatment scores of HRSA were similar in the two groups, older patients improved significantly less than those of group 1 and had also an higher incidence of side-effects. CDDZ levels positively correlated with improvement in group 1 but not in group 2.
已在两组原发性或继发性焦虑症患者中评估了多剂量治疗期间去氯羟安定（氯去甲安定；CDDZ）及其主要代谢物劳拉西泮（LRZ）的动力学。第1组的12名患者年龄为46.8±不到13.2岁，而第2组的8名患者年龄明显更大（69.7±7.8岁）。所有患者均每日两次服用0.5毫克CDDZ，持续30天。通过电子捕获气液色谱法测定研究期间采集的多个血样中CDDZ和LRZ的浓度。焦虑程度根据汉密尔顿焦虑量表（HRSA）进行评估。CDDZ和LRZ在血浆中蓄积，但CDDZ的蓄积速率比年轻志愿者研究预期的要慢，且半衰期值与年龄显著相关。老年患者中葡萄糖醛酸化LRZ的稳态水平也较低。数据表明，随着年龄增长，CDDZ的消除更慢且代谢更少。虽然两组患者治疗前HRSA评分相似，但老年患者的改善明显低于第1组，且副作用发生率也更高。第1组中CDDZ水平与改善情况呈正相关，而第2组中则不然。
