Chambers J H, Fleishaker J C
Clinical Pharmacokinetics Unit, Upjohn Company, Kalamazoo, MI 49001.
Biopharm Drug Dispos. 1994 May;15(4):263-72. doi: 10.1002/bdd.2510150402.
The pharmacokinetics and pharmacodynamics of adinazolam and N-demethyladinazolam (NDMAD) were evaluated in twelve healthy non-smokers (NS) and twelve smokers (S, > or = 20 cigarettes/day) following a single 60 mg dose of adinazolam mesylate sustained-release tablets in an open-label, parallel-group design. Venous blood samples were collected for up to 36 h following drug administration and assayed for adinazolam and NDMAD by HPLC. Urine samples were also collected and assayed for NDMAD by HPLC. Psychomotor performance was measured using the Neurobehavioral Evaluation System. No significant differences were observed in adinazolam oral clearance (51.8 +/- 25.8 versus 48.2 +/- 14.01 h-1) or peak adinazolam plasma concentrations (Cmax) (93.3 +/- 31.8 versus 90.4 +/- 18.0 ng ml-1) between groups. NDMAD AUC (2541 +/- 457 versus 2798 +/- 447 ng h ml-1) and Cmax (173 +/- 30.3 versus 175 +/- 26.9 ng ml-1) did not differ significantly between groups. NDMAD renal clearance was significantly lower in smokers than non-smokers (8.7 +/- 0.7 versus 10.7 +/- 2.71 h-1; p < 0.05), but the clinical significance of this observation is unclear. Marginally significant differences were seen between groups in the symbol-digit substitution and digit span (forward) tasks. The results suggest that smoking has little effect on adinazolam and NDMAD pharmacokinetics or psychomotor effects but that smoking may slightly decrease renal clearance of NDMAD.
在一项开放标签、平行组设计中，对12名健康非吸烟者（NS）和12名吸烟者（S，每天吸烟≥20支）单次服用60mg甲磺酸阿地唑仑缓释片后的阿地唑仑和N - 去甲基阿地唑仑（NDMAD）的药代动力学和药效学进行了评估。给药后长达36小时采集静脉血样，通过高效液相色谱法（HPLC）测定阿地唑仑和NDMAD。还收集尿样并通过HPLC测定NDMAD。使用神经行为评估系统测量精神运动表现。两组之间阿地唑仑的口服清除率（51.8±25.8对48.2±14.01 h-1）或阿地唑仑血浆峰值浓度（Cmax）（93.3±31.8对90.4±18.0 ng/ml）无显著差异。两组之间NDMAD的曲线下面积（AUC）（2541±457对2798±447 ng h/ml）和Cmax（173±30.3对175±26.9 ng/ml）无显著差异。吸烟者的NDMAD肾清除率显著低于非吸烟者（8.7±0.7对10.7±2.71 h-1；p<0.05），但该观察结果的临床意义尚不清楚。在符号数字替换和数字广度（正向）任务中，两组之间观察到轻微显著差异。结果表明，吸烟对阿地唑仑和NDMAD的药代动力学或精神运动效应影响不大，但吸烟可能会略微降低NDMAD的肾清除率。
