卡铂-PECE水凝胶大鼠腹腔药物代谢动力学研究

发布时间：2018-03-15 10:21

  本文选题：卡铂　切入点：PECE水凝胶　出处：《遵义医学院》2014年硕士论文　论文类型：学位论文

【摘要】：目的：将载有卡铂的PECE水凝胶药物缓释系统注入到大鼠腹腔，通过反向高效液相色谱法来测定不同时间段的大鼠血浆中卡铂的浓度，分析其药物代谢动力学特点，旨在为卡铂-PECE水凝胶缓释系统腹腔化疗提供理论依据。 方法：首先制备卡铂-PECE水凝胶，将18只雌性健康的Wistar大鼠随机分为生理盐水组、卡铂组、卡铂-PECE水凝胶组，通过反向高效液相色谱法来测定各组给药后10min、30min、1h、2h、3h及4h大鼠血浆中卡铂浓度，并分析其药物代谢动力学特点，并比较各种给药方式的毒副作用。 结果：卡铂-PECE水凝胶在低温时呈可以注射的溶胶态，在37℃时呈不流动的凝胶态；将卡铂溶液注入到大鼠腹腔后，测定10min、30min、1h、2h、3h及4h卡铂组的血浆药物浓度分别为：0.883±0.0036mg/ml、0.982±0.0051mg/ml、0.499±0.0046mg/ml、0.125±0.0002mg/ml、0.031±0.0006mg/ml、0.007±0.000005mg/ml。卡铂-PECE水凝胶组在相同时间点的药物浓度分别为:0.720±0.0003mg/ml、0.810±0.0023mg/ml、0.615±0.0034mg/ml、0.151±0.0023mg/ml、0.037±0.0002mg/ml、0.0090±0000006mg/ml。比较两组数据，差异有统计学意义（P0.05）。卡铂时间曲线下面积约为1.0940±0.002，卡铂-PECE水凝胶组时间曲线下面积约为1.1116±0.003，比较两组数据，差异有统计学意义（P0.05）。对大鼠重要脏器而言，PECE水凝胶并未增强卡铂的毒副作用。 结论：作为一种可以注射的药物缓释系统，PECE水凝胶具有良好的药物缓释特性，，可以将所装载的抗癌药物-卡铂缓慢地释放到大鼠腹腔进而吸收入血并较长时间维持较高浓度，为卡铂-PECE水凝胶腹腔化疗奠定理论基础。
[Abstract]:Objective: to inject the PECE hydrogel drug delivery system carrying carboplatin into the abdominal cavity of rats, and to determine the concentration of carboplatin in rat plasma at different time intervals by reverse performance liquid chromatography (RHPLC), and to analyze the pharmacokinetic characteristics of carboplatin. To provide theoretical basis for intraperitoneal chemotherapy of carboplatin-PECE hydrogel sustained release system. Methods: carboplatin PECE hydrogels were prepared. Eighteen female healthy Wistar rats were randomly divided into normal saline group, carboplatin group and carboplatin-PECE hydrogel group. The plasma levels of carboplatin were determined by reverse high performance liquid chromatography (RHPLC) in rats at 10 min, 30 min, 1 h, 2 h and 4 h after administration. The pharmacokinetic characteristics of carboplatin were analyzed, and the toxicity and side effects of various drug administration methods were compared. Results: carboplatin-PECE hydrogels showed injectable sol at low temperature and unflowing gel at 37 鈩

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