汉族与侗族受试者地西泮中枢效应的比较

目的: 比较汉族和侗族健康成人服用地西泮(安定)后的中枢神经系统效应,探讨药物作用的种族差异性。方法: 采用双盲随机交叉给药方法,给予汉族和個族受试者各10人以安慰剂、地西泮7.5 mg或15 mg-次口服,所有药丸置于红色胶囊中,各次服药间隔至少2周。受试者检测前均用早餐,检测时间为9:30 am,记录服药前及服药后0.5、1、1.5、2、3、5 h的数字符号匹配试验（DSST)成绩和脑电图。结果: 汉族受试者服7.5 mg地西泮后60~90 min及服15 mg地西泮后30~90 min的血药;农度显著高于侗族受试者,但侗族受试者服15 mg地西泮后3~5 h的血药浓度显著高于汉族受试者,汉族和侗族受试者服用同一剂量5 h后的血药浓度曲线下面积均无显著差异。汉族受试者服15 mg地西泮后1、1.5、3、5 h的DSST下降值和5 h的DSST得分改变曲线下面积均显著低于侗族,经血药浓度校正后这种差异便消失。应用每人的效应一浓度曲线来计算使脑电图快波比重增加50%所需的地西泮浓度,汉族受试者使快波比重增加50 %所需的地西泮血药浓度为 543.8±371.7 μg·L^-1,侗族为 547.0±590.7 μg·L^-1,两民族间无显著性差异。结论: 汉族和個族口服相同剂量地西泮在不同时间的血药浓度有显著性差异,但产生的中枢效应程度相同。

Comparison of central nervous system effect of diazepam on Chinese Han subjects and Chinese Tong subjects

AIM: To compare the central nervous system effect of diazepam on Chinese Han subjects and Chinese Tong subjects. METHODS: Ten subjects of healthy male Tong and ten subjects of healthy male Han were given single oral doses of placebo,7.5 mg diazepam or 15 mg diazepam in a double-blind randomized crossover study. The plasma levels of diazepam, the Digit Symbol Substitution Test (DSST) and the electroencephalographic (EEG) were determined at 0.5, 1, 1.5, 2, 3, and 5 h after administration. RESULTS: The plasma concentra-tions of diazepam in Han subjects were significantly higher than that in Tong subjects at 1-1.5 hours after adminis-tration of 7.5 mg diazepani and at 0.5-1.5 h after ad-ministration of 15 mg diazepam, but they were significant-ly lower at 3-5 houi-s after administration of 15 mg diaze-pam.However, there was no statistical difference between the two ethnic groups in the area under the 5-hour con-centration-time curve after administration of both doses. The decrement of DSST were significantly lower in Han subjects than that in Tong subjects at 1-1.5 h and 3-5 h after administration of 15 mg diazepam, but there was no statistical difference when the decrement of DSST were corrected by the plasma concentrations of diazepam. The individual concentration-response curves were used to cal-culate the concentration of diazepam required to produce a 50 % increase in the percentage of EEG amplitude falling in the range of 12.8 to 31.2 Hz, and there was no signif-icant difference between the Han subjects (543.8±371.7 μg·L^-1) and Tong subjects (547.0±590.7 μg·L^-1) (P>0.05). CONCLUSION: The central nervous system effect of diazepam in Han subjects is simi-lar with that in Tong subjects.