摘要
目的研究丙戊酸在癫痫大鼠的额叶神经药代动力学特征。方法健康雄性SD大鼠12只,随机分成对照组与癫痫组,每组各6只。癫痫组大鼠用印防己碱(PTX)腹腔注射点燃,腹腔注射丙戊酸钠400mg/kg后不同时间点收集两组大鼠额叶细胞外液透析液及血标本。结果丙戊酸迅速吸收入额叶中,在额叶中浓度显著低于血中浓度;癫痫大鼠与正常大鼠额叶的神经药代动力学参数之间的差异无显著性;给药1h后额叶丙戊酸浓度与血清丙戊酸浓度均呈下降趋势。结论癫痫大鼠与正常大鼠额叶丙戊酸神经药代动力学特征相似;丙戊酸在癫痫大鼠额叶的分布可能与额以局部脑血流量变化、血脑屏障功能障碍、丙戊酸穿过血脑屏障需单羧酸(MCA)载体转运等因素有关;监测给药一段时间后血清丙戊酸浓度有助于了解脑卒中后晚发性癫痫患者的额叶丙戊酸浓度,指导临床合理用药。
Objective To explore the neuropharmacokinetic character of valproate(VPA) in epileptic rat frontal cortex extracellular fluid(ECF). Methods Twelve healthy male SD rats were divided to normal group and epileptic group randomly, each group six rats. Epileptic group rats were kindled by picrotoxin intraperitoneal injection. After intraperitoeal injection of VPA 400 mg/kg, ECF samples of frontal cortex and blood sample were collected of both groups in different time point. Results VPA was rapidly uptaken into brain, VPA concentration in rat brain was lower than that in serum; There was no significant difference in neuropharmacokinetic parameter between epileptic rat and normal rat; After first 60 minute administration both brain ECF and serum's VPA concentration displayed a stable decreasing tendency. Conclusion VPA pharmacokinetic character of epileptic rat brain was similar to that of normal rat brain; the distribution in frontal cortex was connected with the change of blood flow, the damagement of blood brain barrier (BBB), the number of monocarboxylic acid (MCA) carrier in capillary endothelium of frontal cortex; Monitor patient's serum valproate (VPA) concentration time course after a certain time administration can indirectly reflect frontal cortex's VPA concentration change in patients after stroke, which provided evidence for clinical administration.
出处
《中国临床康复》
CSCD
2002年第23期3578-3579,共2页
Chinese Journal of Clinical Rehabilitation
关键词
丙戊酸
癫痫
大鼠
额叶
神经药代动力学
epilepsy
stroke
frontal cortex
valproate
pharmacokinetics
