BACKGROUND: 5-fluorouracil (5-Fu) is universally used as an antineoplastic agent in gastrointestinal cancer, but the side effect of it confined further clinical application. OBJECTIVE: To determinate mice plasma concentration curves for 5-Fu and its chitosan (CS)-polyaspartic acid (Pasp) nanoparticles, and to investigate their primary pharrnacokinetics. DESIGN, TIME AND SETTING: Randomization control animal trials were performed in the Department of Gastroenterology, Zhongshan Hospital of Fudan University between October 2006 and June 2007. MATERIALS: Totally 180 female Kunming mice were obtained from the Department of Laboratory Animal, Fudan University. 5-Fu (purity 99%) was purchased from Shanghai Xudong Haipu Pharmaceutical Co, Ltd (Shanghai, China). Two kinds of CS-Pasp-5-Fu particles were offered by Department of Macromolecular Science, Key Laboratory of Molecular Engineering of Polymers of Educational Ministry, Fudan University (Shanghai, China). METHODS: Kunming mice were randomly divided into three groups and each group was administrated with 5-Fu or either type of its CS-Pasp-5-Fu nanoparticlos. The plasma concentrations of 5-Fu were evaluated by high performance liquid chromatography after 15 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 16 hours, 24 hours and 48 hours of the administration. The pharmacokinetic parameters were computed utilizing 3P97. MAIN OUTCOME MEASURES: Relative recovery, absolute recovery and the stability of samples. RESULTS: The peak concentration of 5-Fu group occurred within 15 minutes and then decreased rapidly. The No.1 nanoparticles group's peak concentration occurred 6 hours after the administration and the effective concentration time lasted for about 14 hours. No.2 nanoparticles group's concentration curve was double-apex, the apexes occurred around the 2 hours and 16 hours, the concentration decreased at the 24 hours after the administration. Both of the two kinds of the nanoparticles groups' peak concentration of 5-Fu in plasma are lower than the 5-Fu group, The half-life times were prolonged and the areas under curve were higher. CONCLUSION: Compared to 5-Fu, the CS-Pasp-5-Fu nanoparticles are controlled released.%背景:5-氟尿嘧啶(5-Ruorouracil,5-Fu)是最常用的消化道肿瘤化疗药物之一,但是其副作用却限制了它进一步临床应用.目的:5-Fu原药及其壳聚精(chitosan,CS)-聚天冬氨酸(polyaspartic acid,Pasp)纳米粒子小鼠灌胃后血药浓度曲线及其药代动力学初步研究,了解5-Fu经纳米包载后是否具有缓释作用.设计、时间及地点:随机对照动物实验,于2006-10/2007-06在中山医院消化科实验室完成.材料:健康雌性昆明小鼠180只由复旦大学动物实验中心提供.5-Fu(纯度99%)由上海旭东海普药业有限公司提供.2种CS-Pasp-5Fu纳米粒子山复旦大学高分子科学系聚合物工程教育部重点实验室制备.方法:同性健康昆明小鼠分为3组,分别予5-Fu原药及其2种CS-Pasp-5Fu纳米粒子灌胃.灌胃后15min,1,2,4,6,8,12,16,24和48 h 10个时间点取血.高效液相色谱法测其血药浓度,代入3P97程序计算各样品的药代动力学参数并作比较.主要观察指标:相对回收率,绝对回收率,样品稳定率.结果:5-FU原药组的药物峰浓度出现在灌胃后15 min之内,此后血药浓度迅速降低.CS-Pasp-5Fu纳米粒子1组的药物峰浓度出现在灌胃后6 h左右,并在14 h内维持较高的浓度.cs-Pasp-5Fu纳米粒子2组的血药浓度曲线呈双峰形,药物峰浓度分别出现在灌胃后2 h和16 h左右,24 h后下降.与5-Fu原药相比,2种CS-Pasp-5Fu纳米粒子的血药峰浓度(Cmax)降低,半衰期(T1/2)延长,血药浓度时间曲线下面积明显增加.结论:CS-Pasp-5FU纳米粒子具有缓释作用.
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