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红景天苷在大鼠悬尾模型中的药代动力学研究
引用本文:邵淑容,董辉,李亚东,刘正,曲卫敏. 红景天苷在大鼠悬尾模型中的药代动力学研究[J]. 复旦学报(医学版), 2016, 43(4): 393-400,420. DOI: 10.3969/j.issn.1672-8467.2016.04.003
作者姓名:邵淑容  董辉  李亚东  刘正  曲卫敏
作者单位:1 复旦大学基础医学院药理学系, 2 医学神经生物学国家重点实验室 上海 200032; 3 绍兴文理学院医学院药理学系 绍兴 312000; 4 复旦大学脑科学研究院与协同创新中心 上海 200032
基金项目:supported by the National Program on Key Basic Research Project of China(2011CB711000);the National Natural Science Foundation of China(31471064);the Science&Technology Planning Project of Shaoxing City,China(2014A230109)~~
摘    要: 目的  采用大鼠悬尾模型模拟失重状态,研究红景天苷在微重力状态下的药代动力学变化。方法  建立大鼠悬尾模拟微重力模型,分别在第1、2和5天灌胃给予红景天苷 (100 mg/kg),HPLC法检测红景天苷血药浓度。结果  血浆中加红景天苷标准品,在流动相 (甲醇:水=80∶20,流速为1 mL/min)中的保留时间为5.96 min。红景天苷浓度在1~100 μg/mL线性相关性良好 (r=0.999 9),最低检测限为1 μg/mL。对红景天苷浓度为2、10、50 μg/mL的质控样品溶液进行精密度和准确度评价,日内、日间误差均≤15%。血浆样品的平均回收率均≥90%。与对照组相比,悬尾5天的大鼠灌胃给药后,红景天苷的血浆峰浓度和药时曲线下面积分别增加63%和36%;药物清除率减少24.81%。而悬尾1天和悬尾2天的大鼠给药后未见差异。结论  悬尾模拟微重力增加红景天苷在大鼠体内的分布,降低清除速度,提示在太空服用该药物时可能需要调整剂量。

关 键 词:药代动力学  大鼠  红景天苷  模拟微重力  悬尾
收稿时间:2016-01-13

Pharmacokinetics of salidroside in a tail-suspended rat model
SHAO Shu-rong;DONG Hui;LI Ya-dong;LIU Zheng;QU Wei-min. Pharmacokinetics of salidroside in a tail-suspended rat model[J]. Fudan University Journal of Medical Sciences, 2016, 43(4): 393-400,420. DOI: 10.3969/j.issn.1672-8467.2016.04.003
Authors:SHAO Shu-rong  DONG Hui  LI Ya-dong  LIU Zheng  QU Wei-min
Affiliation:1 Department of Pharmacology, 2 State Key Laboratory of Medical Neurobiology,School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; 3 Department of Pharmacology, Medical College of Shaoxing University, Shaoxing 312000, Zhejiang Province, China; 4 Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China
Abstract:Objective  To measure the salidroside′s pharmacokinetics in a simulated weightlessness rat model. Methods  Rats were given salidroside (via gavage,100 mg/kg) on the 1st,2nd,and 5th day of tail-suspension.Pharmacokinetic parameters were measured by HPLC. Results  Plasma retention of salidroside was 5.96 min in a methanol and water (80∶20) mobile phase (flow 1 mL/min).When salidroside concentrations ranged from 1 to 100 μg/mL,they were clinically relevant (r=0.999 9),and quantification limits were 1 μg/mL in rat plasma.The within- and between-day errors were less than 15% in quality control samples of salidroside at 2,10 and 50 μg/mL,respectively.Salidroside mean recovery exceeded 90% in rat plasma.On the 5th day of tail-suspension rats,peak concentration (Cmax) and area under the curve (AUCs) for salidroside increased by 63% and 36%,respectively,and clearance rate of salidroside decreased by 24.81%,as compared with control.While no change was  found in tail-suspension rats on the 1st day and 2nd day. Conclusions  Simulated weightlessness significantly increased distribution and decreased clearance rate of oral salidroside in rats,suggesting that the dosage of salidroside should be modified when used in the space flight.
Keywords:pharmacokinetics  rats  salidroside  simulated weightlessness  tail-suspension
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