Ghoneim M M, Korttila K, Chiang C K, Jacobs L, Schoenwald R D, Mewaldt S P, Kayaba K O
Clin Pharmacol Ther. 1981 Jun;29(6):749-56. doi: 10.1038/clpt.1981.106.
Mental and psychomotor effects and diazepam kinetics were studied in Caucasian and Orientals. 12 Caucasian and 13 Oriental young adults received on one of two occasions, separated by 2 weeks, either 0.2-mg/kg diazepam or saline intravenously. Serum diazepam and desmethyldiazepam concentrations were measured by electron-capture gas-liquid chromatography in samples drawn up to 72 hr after injection. Serum protein binding was measured by equilibrium dialysis. Subjects were tested on a battery of psychological tests before and 0.5, 2, and 4 hr after treatment. While the free fraction of diazepam was identical in both races (0.02), volume of distribution at steady state (Vdss) was different when calculated as absolute volume (Vdss = 76.55 +/- 9.63 l in Caucasians and 54.96 +/- 4.55 l in Orientals, p = 0.04) and marginally significant when corrected for body weight (Vdssl/kg = 1.10 +/- 0.11 in Caucasian and 0.88 +/- 0.05 in Orientals, p = 0.07). total body clearance (Cl), but not elimination half-life (t 1/2), was higher in Caucasians than Orientals, p less than 0.01; t 1/2 = 37.70 +2- 5.53 hr in Caucasians and 41.77 +/- 3.80 in Orientals). Desmethyldiazepam levels were higher in Orientals than Caucasians. Mental and psychomotor effects were maximal at the first session (0.5 hr), followed by complete recovery by the 4-hr session. Effects were similar in both groups. If repeated dosing causes a higher rate of cumulated diazepam serum levels in Orientals, as expected, there might be deeper brain depression in that group.
对高加索人和东方人的精神及精神运动效应以及地西泮动力学进行了研究。12名高加索和13名东方年轻成年人在两个场合之一接受了静脉注射，两次场合间隔2周，分别注射0.2mg/kg地西泮或生理盐水。在注射后长达72小时采集的样本中，通过电子捕获气液色谱法测量血清地西泮和去甲地西泮浓度。通过平衡透析法测量血清蛋白结合率。在治疗前以及治疗后0.5、2和4小时，对受试者进行了一系列心理测试。虽然地西泮的游离分数在两个种族中相同（0.02），但当以绝对体积计算时，稳态分布容积（Vdss）不同（高加索人为76.55±9.63L，东方人为54.96±4.55L，p = 0.04），校正体重后差异边缘显著（高加索人为1.10±0.11，东方人为0.88±0.05，p = 0.07）。高加索人的总体清除率（Cl）高于东方人，但消除半衰期（t1/2）无差异，p<0.01；高加索人的t1/2为37.70±5.53小时，东方人为41.77±3.80小时。东方人的去甲地西泮水平高于高加索人。精神和精神运动效应在第一阶段（0.5小时）最大，随后在4小时阶段完全恢复。两组效应相似。如果如预期那样重复给药导致东方人地西泮血清水平累积率更高，那么该组可能会出现更深的脑抑制。
