苯妥英钠在大鼠血液和脑细胞外液药动学研究  

Pharmacokinetics of Phenytoin in Rat Blood and Extracellular Fluids of Brain

作　　者：马爱梅[1] 赵永波[1] 陈英辉[1] 

机构地区：[1]上海交通大学附属第一人民医院神经科,200080

出　　处：《中国临床神经科学》2005年第2期118-122,共5页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金资助项目 (30 370 51 1 );上海市引进海外高层次留学人员专项基金资助项目 (2 0 0 4 1 5)

摘　　要：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。Aim:To investigate the pharmacokinetic parameters of phenytoin in serum and cxtraccllular fluids in hippocampus and frontal cortex of rats.Methods:We used microdialysis and high-performance liquid chromatography (HPLC) in this research,after intraperitoneal injection of phenytoin 50 mg·kg -1 and 100 mg·kg -1 ,the blood and microdialysis samples were collected at time intervals up to 3 hours ,and the concentration of phenytoin in serum and brain extracellular fluids were determined at each time point.Results:The concentration of phenytoin in serum is much higher in 100 mg·kg -1 group than 50 mg·kg -1 group ( P <0.05),the concentration of phenytoin in extracellular fluids in hippocampus is higher than frontal cortex both in 100 mg·kg -1 group than 50 mg·kg -1 group,but it does not show significant difference.Conclusion:Phenytoin crossed the blood-brain barrier rapidly,the maxium concentration( T _ max )was reached during 60～90 min after injection. The area under the concentration-time curve was higher in hippocampus than in frontal cortex.The t _ 1/2 was longer in hippocampus than in pharmacokinetics of phenytoin in brain extracellular fluids ,but after 60 min by administration,the decline tendency in serum could reflect the decrease of concentration of phenytoin in brain extracellular fluids.

关 键 词：苯妥英钠 药动学研究 脑细胞外液 大鼠血液 高效液相色谱技术 药时曲线下面积 腹腔注射 药物浓度 大鼠血浆 血药浓度 海马神经元 大鼠脑组织 海马内 不同时间 大脑皮质 药物清除 浓度变化 脑内 微透析 给药 统计学 峰浓度 

分 类 号：R971.6[医药卫生—药品] R969.1[医药卫生—药学]