卡马西平在大鼠血液和脑细胞外液中药代动力学研究  

Pharmacokinetics of Carbamazepine in Blood and Extracellular Fluids of Brain in Rat

作　　者：马爱梅[1] 牛争平[2] 

机构地区：[1]山西省人民医院 [2]山西医科大学第一医院

出　　处：《中西医结合心脑血管病杂志》2009年第3期309-312,共4页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：山西省青年科技研究基金资助项目(No.2006021044)

摘　　要：目的分析卡马西平在大鼠血浆和脑内药代动力学的变化。方法采用微透析活体取样技术和高效液相色谱技术,通过腹腔注射卡马西平20mg/kg和40mg/kg,测定给药后3h内不同时间点大鼠血浆、大脑皮层和海马神经元细胞外液的药物浓度。结果腹腔注射40mg/kg卡马西平血药浓度显著高于20mg/kg(P<0.05),腹腔注射20mg/kg和40mg/kg卡马西平后各时间点海马内药物浓度高于皮层(P<0.05)。结论卡马西平迅速进入大鼠脑组织,给药后90min～120min达峰浓度。海马内药时曲线下面积大于皮层,说明给药后海马内药物浓度高于皮层。腹腔注射卡马西平后90min内,血药浓度变化不能反映药物在脑内的代谢趋势,90min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 investigate the pharmacokinetic parameters of carbamazepine in serum and extracellular fluids of hippocampus and frontal cortex in rats. Methods Microdialysis and high - performance liquid chromatography （HPLC） were used in this research. After intraperitoneal injection of carbamazepine 20 mg/kg and 40 mg/kg,the blood and microdialysis samples were collected and the concentration of carbamazepine in serum and brain extracellular fluids were determined. Results The concentration of carbarnazepine in serum was much higher in 40 mg/kg group than that in 20 mg/kg group （P〈0.05）. The concentration of carbamazepine in extracellular fluids of hippocampus was higher than that in frontal cortex in 40 mg/kg group and 20 mg/kg group （P〈0.05）. Conclusion Carbamazepine was crossed the blood- brain harrier rapidly,the maximum concentration （Tmax） was reached during 90 min to 120 rain after injection. The area under the concentration - time curve was higher in hippocampus than in frontal cortex. In the first 90 min after injection, the concentration in serum might not reflect the pharmacokinetics Of carbamazepine in brain extracellular fluids. After 90 min after administration, the decline tendency in serum could reflect the decrease of concentration of carbamazepine in brain extracellular fluids.

关 键 词：卡马西平 药代动力学 微透析 高效液相色谱 

分 类 号：R96[医药卫生—药理学]