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3种剂量9-硝基喜树碱大鼠单次灌胃给药后的药动学研究
引用本文:张春燕,殷琦,李玉珍,李长龄.3种剂量9-硝基喜树碱大鼠单次灌胃给药后的药动学研究[J].中国药学杂志,2005,40(11):852-854.
作者姓名:张春燕  殷琦  李玉珍  李长龄
作者单位:1. 北京大学人民医院药剂科,北京,100044
2. 北京医院药剂科,北京,100730
3. 北京大学药理系,北京,100083
摘    要: 目的建立测定血浆中9-硝基喜树碱的反相高效液相色谱法,研究其在大鼠体内的药动学规律及特点。方法SD大鼠单次灌胃9-硝基喜树碱后于不同时间点自眼眶后静脉丛取血,用HPLC测定其血药浓度,用DAS(1.0)软件计算药动学参数。结果血药达峰浓度cmax随给药剂量的递增而递增(2 mg·kg-1组为653.02 ng·mL-1,3 mg·kg-1组为832.9 ng·mL-1,5 mg·kg-1 组为2 731.15 ng·mL-1),达峰时间tmax不随给药剂量增加而延长(2 mg·kg-1组为0.32 h,3 mg·kg-1组为0.45 h,5 mg·kg-1组为0.3 h),药时曲线下面积AUC0-∞随剂量递增而增加(2 mg·kg-1组为856.49μg·h·L-1,3 mg·kg-1组为1 485.69μg·h·L-1, 5 mg·kg-1组为3 995.39μg·h·L-1)。结论3种剂量9-硝基喜树碱大鼠单次灌胃后的药动学参数显示其在大鼠体内转化或消除均较快,呈一房室模型,药物的体内过程表现为线性药动学特征。

关 键 词:9-硝基喜树碱  药动学
文章编号:1001-2494(2005)11-0852-03
收稿时间:2004-06-10;

Pharmacokinetics of 9-nitrocamptothecin after single oral administrations in rats
ZHANG Chun-yan,YIN Qi,LI Yu-zhen,LI Chang-ling.Pharmacokinetics of 9-nitrocamptothecin after single oral administrations in rats[J].Chinese Pharmaceutical Journal,2005,40(11):852-854.
Authors:ZHANG Chun-yan  YIN Qi  LI Yu-zhen  LI Chang-ling
Institution:1.Department of Pharmacy,People’s Hospital,Peking University, Beijing 100044,China; 2.Department of Pharmacy, Beijing Hospital,Beijing 100730,China;3.Department of Pharmacology,School of Pharmacology,Peking University, Beijing 100083,China
Abstract:OBJECTIVE To develop a reversed phase high performance liquid chromatographic method for the determination of 9-nitro-camptothecin in plasma and to investigate the pharmacokinetics of 9-nitroeamptotheein at three doses in rats. METHODS Venous blood was collected from eyehole after a single oral administration of 9-nitrocamptothecin. The plasma concentrations of 9-nitroeamptothecin were measured using HPLC, pharmacokinetic parameters were calculated by DAS( 1.0) .RESULTS The main pharmacokinetic parameters were:cmax 653.02ng·mL-1(2mg·kg-1), 832.9 ng·mL-1(3 mg·kg-1 ) and 2 731.15 ng·mL-1 (5 mg·kg-1); tmax0.32 h (2 mg·kg-1) , 0.45 h (3 mg·kg-1) and0.3h(5mg·kg-1); AUC0-∞ 856.49 μg·h·L-1(2 mg·kg-1), 1 485.69 μg·h·L-1(3 mg·kg-1) and 3 995.39 μg·h·L-1(5 mg·kg-1) .CONCLUSION The parent compound was metahlised or eliminated quickly. The plasma concentration-time curve of 9-nitrocamptothecin was fitted with an one-compartment open pharmacokinetic model and appeared to be a linear pharmacokinetic characteristics.
Keywords:9-nitrocamptothecin  pharmacokinetics
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