Hulhoven R, Desager J P, Cox S, Harvengt C
Laboratoire de Pharmacothérapie, Université Catholique de Louvain, Bruxelles, Belgium.
Eur J Clin Pharmacol. 1988;35(1):59-64. doi: 10.1007/BF00555508.
Adinazolam is a new triazolobenzodiazepine bearing an alkyl-amino side chain. A cross-over double-blind placebo controlled study was carried out in 12 healthy volunteers, in order to check the possible interaction between cimetidine and adinazolam after repeated co-administration. Cimetidine or placebo were given during 17 days. Beginning on Day 8 of each treatment, adinazolam was given in the increasing doses following sequence of doses for 3 days: 10 mg b.i.d., 20 mg b.i.d. and 20 mg t.i.d. A pharmacokinetic and pharmacodynamic study was performed on the third day at each dose. A wash-out of three weeks was included between the two treatments. Cimetidine increased significantly the AUC values of both adinazolam and N-desmethyladinazolam, reduced the oral clearance of adinazolam, and prolonged adinazolam's half-life. The digit symbol substitution test was significantly affected at each dose level while the manual dexterity was marginally impaired by adinazolam plus cimetidine. Saftee-up interview and Clyde mood scale indicated an increased sedation under adinazolam plus cimetidine in four subjects.
阿地唑仑是一种带有烷基氨基侧链的新型三唑并苯二氮䓬。在12名健康志愿者中进行了一项交叉双盲安慰剂对照研究，以检查西咪替丁与阿地唑仑反复联合给药后可能存在的相互作用。西咪替丁或安慰剂连续服用17天。从每种治疗的第8天开始，按照剂量递增顺序给予阿地唑仑，持续3天：10毫克，每日两次；20毫克，每日两次；20毫克，每日三次。在每个剂量的第三天进行了药代动力学和药效学研究。两种治疗之间有三周的洗脱期。西咪替丁显著增加了阿地唑仑和N-去甲基阿地唑仑的AUC值，降低了阿地唑仑的口服清除率，并延长了阿地唑仑的半衰期。在每个剂量水平，数字符号替换测试均受到显著影响，而阿地唑仑加西咪替丁对手动敏捷度有轻微损害。安全访谈和克莱德情绪量表显示，在四名受试者中，阿地唑仑加西咪替丁会增加镇静作用。
