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目的:分析苯妥英钠在大鼠血浆和脑内药动学变化。方法:采用微透析活体取样和高效液相色谱技术,通过腹腔注射苯妥英钠5 0和10 0mg·kg-1,测定给药后3h内不同时间点大鼠血浆、大脑皮质和海马神经元细胞外液的药物浓度。结果:腹腔注射苯妥英钠10 0mg·kg-1血药浓度显著高于5 0mg·kg-1(P <0 .0 5 ) ,腹腔注射苯妥英钠5 0和10 0mg·kg-1后各时间点海马内药物浓度高于皮质,但统计学比较无显著差异。结论:苯妥英钠迅速进入大鼠脑组织,给药后60～90min达峰浓度。海马内药时曲线下面积略大于皮质,说明给药后海马内药物浓度高于皮质。苯妥英钠半衰期海马长于皮质,说明海马内药物清除速度较慢。腹腔注射苯妥英钠后60min内,血药浓度变化不能反映药物在脑内的代谢趋势,60min后血药浓度降低的速度在一定程度上可以反映脑内药物浓度减低的趋势。
Objective: To analyze the pharmacokinetics of phenytoin in rats plasma and brain. Methods: Micro-dialysis in vivo and high performance liquid chromatography (HPLC) were used to measure the plasma, cerebral cortex and hippocampal neurons of rats at different time points within 3h after intraperitoneal injection of 50 and 100 mg · kg-1 of phenytoin Liquid drug concentration. Results: The plasma concentration of phenytoin 10 0 mg · kg-1 was significantly higher than that of 50 mg · kg-1 (P <0.05), and the intraperitoneal injection of phenytoin 50 and 100 mg · kg-1 The concentration of drug in the hippocampus was higher than that in the cortex, but there was no significant difference in statistics. Conclusion: Phenytoin rapidly enters rat brain tissue and reaches the peak concentration of 60-90 min after administration. The area under the curve of the hippocampus was slightly larger than that of the cortex, indicating that the concentration of the drug in the hippocampus was higher than that in the cortex after administration. Phenytoin half-life hippocampus longer than the cortex, indicating that drug clearance in the hippocampus is slower. Intraperitoneal injection of phenytoin within 60min, the change of plasma concentration can not reflect the metabolic trend of drug in the brain, 60min plasma concentration decreased to a certain extent, the rate of drug concentration in the brain can reflect the trend.