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吲哚美辛对5-氟尿嘧啶在大鼠体内药代动力学的影响
引用本文:钱瑾,吴慧哲,詹丽芬. 吲哚美辛对5-氟尿嘧啶在大鼠体内药代动力学的影响[J]. 中国药理学与毒理学杂志, 2005, 19(6): 455-457
作者姓名:钱瑾  吴慧哲  詹丽芬
作者单位:中国医科大学基础医学院药理学教研室,辽宁,沈阳,110001
摘    要:目的探讨吲哚美辛(Ind)增强5-氟尿嘧啶(5-Fu)的抗肿瘤作用是否与药代动力学的变化有关。方法采用反相高效液相色谱(HPLC)法测定大鼠血浆中5-Fu浓度,数据用“3p97”程序处理。结果单用和联用Ind后,5-Fu在大鼠体内的药代动力学均为一室模型,t1/2ka分别为(3.8±2.0)和(4.4±2.7)min,t1/2ke分别为(57±46)和(101±48)min,ke分别为(0.018±0.010)和(0.009±0.005)min-1,cmax分别为(7.0±1.8)和(19±8)mg.L-1,AUC分别为(0.7±0.5)和(3.5±2.4)g.min.L-1,Cl分别为(100±50)和(24±21)mg.kg-1.min-1。说明联用Ind后,5-Fu的作用时间延长,在大鼠体内的经时过程增长。结论Ind能延缓5-Fu在大鼠体内的消除,两者联用时应注意调整给药剂量和对5-Fu进行临床给药监测。

关 键 词:5-氟尿嘧啶  吲哚美辛  药代动力学
收稿时间:2005-01-19
修稿时间:2005-07-20

Effect of indometacin on pharmacokinetics of 5-fluorouracil in rats
QIAN Jin,WU Hui-Zhe,ZHAN Li-Fen. Effect of indometacin on pharmacokinetics of 5-fluorouracil in rats[J]. Chinese Journal of Pharmacology and Toxicology, 2005, 19(6): 455-457
Authors:QIAN Jin  WU Hui-Zhe  ZHAN Li-Fen
Affiliation:(Department of Pharmacology,College of Basic Medical Sciences, China Medical University, Shenyang 110001,China)
Abstract:AIM To study whether the enhancing effect of indometacin(Ind) on antitumor action of 5-fluorouracil(5-Fu) is related to the change in the pharmacokinetics of 5-Fu. METHODS The plasma concentrations of 5-Fu were determined by reverse phase high performance liquid chromatography and analyzed by “3p97” pharmacokinetic program. RESULTS The plasma drug concentration-time curves of 5-Fu in rats fit the one-compartment model. The pharmacokinetic parameters of 5-Fu alone and combined with Ind were: t1/2ka, (3.8±2.0), (4.4±2.7)min; t1/2ke, (57±46), (101±48)min; ke, (0.018±0.010), (0.009±0.005)min-1; cmax, (7.0±1.8), (19±8)mg·L-1; AUC, (0.7±0.5), (3.5±2.4)g·min·L-1; and Cl, (100±50), (24±21)mg·kg-1·min-1, respectively. The results suggested that the action time of 5-Fu be prolonged and the elmination be delayed when Ind was used in combination. CONCLUSIONIt is necessary to adjust the therapeutic dose of 5-Fu and put up the monitoring of plasma drug concentration when combined with Ind.
Keywords:5-fluorouracil  indometacin  pharmacokinetics  
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