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目的探讨丙戊酸在正常及癫大鼠海马神经元间隙液中的神经药物动力学过程。方法建立大鼠慢性癫模型及自由活动的清醒动物脑内在体微透析模型,结合荧光偏正免疫分析法测定急性腹腔注射丙戊酸(200mg/kg)后该药在大鼠海马胞外的动力学过程。用3P87药物动力学程序对药浓时间数据进行拟合。结果丙戊酸在正常及癫大鼠海马胞外的峰浓度(cmax)与药时曲线下面积(AUC0→∞)分别为(93.09±54.82)、(235.3±93.2)μg/mL及(6252±3607)、(19286±5219)μg·min·mL-1(n=5)。结论推测由戊四氮诱发的大鼠脑病理性改变可能导致了丙戊酸在癫大鼠海马的蓄积,该研究为丙戊酸的临床抗癫治疗提供了新的实验资料。
Objective To investigate the neuropharmacokinetic process of valproate in hippocampal neurons of normal and epileptic rats. Methods A rat model of chronic epilepsy and free intracerebral microdialysis model of conscious animals was established. Fluorescence partial ionization immunoassay was used to determine the effect of intraperitoneal injection of valproic acid (200 mg / kg) Kinetic process. The 3P87 pharmacokinetic program was used to fit the drug concentration time data. Results The peak area (cmax) and the area under the curve (AUC0 → ∞) of valproic acid in normal and epileptic rat hippocampus were (93.09 ± 54.82), (235.3 ± 93.2) μg / mL and ± 3607), (19286 ± 5219) μg · min · mL-1 (n = 5). Conclusions The hypothesis that pentylenetetrazole-induced pathological changes in rat brain may lead to the accumulation of valproic acid in the hippocampus of epileptic rats provides a new experimental data for clinical anti-epileptic treatment of valproic acid.