【摘要】 【目的】比较表面活性剂普朗尼克P85和维拉帕米对传统抗癫痫药物苯妥英钠的脑靶向分布作用。【方法】健康雌性Sprague-Dawley大鼠,25只,周龄9~10周,体质量190~240 g,随机分为5组,每组5只。具体为PHT组、+VPM组、+0.1%P85组、+1%P85组、+10%P85组。PHT组静脉注射苯妥英钠;+VPM组静脉注射苯妥英钠前30 min腹腔注射维拉帕米;+0.1%P85组、+1%P85组和+10%P85组静脉注射的苯妥英钠用相应浓度的普朗尼克P85溶液配制。给予苯妥英钠后分别在不同时间点取大脑微透析液和血液,最后处死大鼠分离肝脏和肾脏组织。高效液相色谱法检测各样本中苯妥英钠的浓度,评估苯妥英钠的脑靶向分布情况。【结果】+10%P85组、+1%P85组、+0.1%P85组和+VPM组与PHT组比较,脑组织间液和血浆苯妥英钠的曲线下面积比值分别提高113.5%、50.4%、21.9%和7.2%,各组之间两两比较差异均有统计学意义。+VPM组苯妥英钠药物浓度肝血比明显升高,与其余各组之间差异有统计学意义。各组苯妥英钠药物浓度肾血比之间比较,差异无统计学意义。【结论】相对于维拉帕米,普朗尼克P85可明显的提高苯妥英钠进入大脑的剂量,而且不会提高苯妥英钠在肝脏和肾脏的累积分布,具有脑靶向输送作用。更多还原

【Abstract】 【Objective】 Attempt to explore the effect of surfactant Pluronic P85 on brain-targeted distribution of traditional antiepileptic drugs phenytoin compared with verapamil.【Methods】 Healthy female SD rats of aged of 6 ~ 8 weeks,weight of 200 ~ 240 g were randomly divided into PHT group,+VPM group,0.1% P85+PHT group,1% P85+PHT group and 10% P85+PHT group(n = 5).Several dialysate and blood samples of different times were collected after PHT administration.Major organs such as the liver and kidney were removed for tissues distribution study.Concentrations of PHT of different samples were detected by high performance liquid chromatography(HPLC) to evaluate the brain-targeted distribution of phenytoin.【Results】 Compared with the PHT group,the PHT AUC ratios between brain extracellular fluid and plasma in 10% P85+PHT group,1% P85+PHT group,0.1% P85+PHT group and +VPM group,were significantly increased by 113.5%,50.4%,21.9%,and 7.2%(P < 0.05),respectively.The hepatic blood ratio in liver homogenate in +VPM group was significantly higher than any other group(P < 0.05).The differences of renal blood ratio between either two groups were not statistically significant.【Conclusion】 Pluronic P85 could significantly increase the concentration of PHT into the brain,and would not enhance the PHT cumulative distribution in liver and kidney,relatively to the Pgp antagonist of VPM.更多还原