氯硝西泮单次给药与重复给药的实验研究

目的:研究氨硝西泮在大鼠血清及脑组织药物浓度的动态变化。方法:采用高效液相色谱法(HPLC)测定药物浓度,色谱柱为C18柱(200mm×4.6mm,4μm),流动相为甲醇∶水(55∶45),流速:0.8ml/min,检测波长310nm,柱温25℃。对48只健康成年SD大鼠血清及脑匀浆上清液经氯仿提取,挥干,用流动相重溶,进行色谱分析。结果:单次给药后大鼠血清及脑组织药物浓度快速下降,尤其是脑组织;重复给药后,血清及脑组织药物浓度再次升高。结论:氯硝西泮血清及脑组织中药物浓度的快速下降,可以导致惊厥复发。氯硝西泮重复给药可有效地控制惊厥复发,但也可引起药物在体内的蓄积。

An experimental study on single and repeated-dose administration of clonazepam

Objective: To study the dynamic change of clonazepam's concentration in the serum and brain of rat. Methods : High pressure liquid chromatography was used to detect the concentration of clonazepam, with Kromasil C18 column as stationary phase, methanol-water(55: 45) as mobile phase with the flow rate of 0. 8ml/min. The temperature of column was 25℃; the wavelength of detection was 310nm. Clonazepam was extracted from serum and brain of forty-eight healthy SD rats by chloroform and solved in mobile phase. Results: In single dose group, the concentration of CZP decreased rapidly, especially in brain. Repeated administration of CZP at 30 min maintained a high concentration in serum and brain for a relatively long time. Conclusion: The rapid decrease of the concentration of clonazepam was the reason for seizure relapse. Repeated administration of CZP would avoid this, but might lead to drug accumulation in the body.