静脉注射乌苯美司/5-氟尿嘧啶在大鼠体内的药动学研究  

Pharmacokinetic Study of Bestatin/5-Fluorouracil in Rats with Intravenous Administration

作　　者：荆凡波[1] 徐文[1] 龚伟玲[2] 刘东华[1] 隋忠国[1] 

机构地区：[1]青岛大学附属医院,山东青岛266003 [2]青岛大学医学院2011级研究生,山东青岛266071

出　　处：《中国药房》2015年第1期26-29,共4页China Pharmacy

基　　金：山东省自然科学基金资助项目(No.ZR2011HQ032)

摘　　要：目的:建立大鼠静脉注射乌苯美司/5-氟尿嘧啶(Bes/5-FU)后血药浓度的检测方法,并研究其药动学特征。方法:取6只大鼠股静脉注射Bes/5-FU生理氯化钠溶液84 mg/kg,给药后0.033、0.083、0.167、0.333、0.5、1、2、3、4、6、8、10 h经眼底静脉丛取血,高效液相色谱法分别检测Bes/5-FU和5-FU的血药浓度,用DAS 2.0分析软件计算给药后代谢产物5-FU的药动学参数。色谱柱为Venusil ASB C18,流动相为乙腈-0.05%甲酸(22∶78)(Bes/5-FU)、甲醇-水(5∶95)(5-FU),流速为1 ml/min,检测波长为262.7 nm(Bes/5-FU)、266 nm(5-FU),柱温为25℃,进样量为30μl(Bes/5-FU)、20μl(5-FU)。结果:Bes/5-FU给药后2 h在大鼠体内已基本代谢完全。5-FU药动学参数t1/2为(0.14±0.04)h,MRT0-10 h为(0.17±0.04)h,AUC0-10 h为(17.73±6.27)μg·h/ml,AUC0-∞为(17.78±6.31)μg·h/ml。结论:本方法可快速、准确地检测Bes/5-FU及其代谢产物5-FU在大鼠体内的血药浓度;Bes/5-FU在大鼠体内迅速代谢为5-FU。OBJECTIVE： To establish a method for determining plasma concentrations of Bestatin （Bes）/5-Fluorouracil （5- FU）, and to study its pharmacokinetic characteristics. METHODS： 6 rats were given Bes/5-FU sodium chloride solution 84 mg/kg via femoral vein. Plasma samples were collected from retinal vein plexus 0-033, 0.083, 0.167, 0.333, 0.5, 1, 2, 3, 4, 6, 8 and 10 h after medication. The plasma concentrations of Bes/5-FU and 5-FU were detected with HPLC, and DAS 2.0 software was used to calculated the main pharmacokinetics parameters of 5-FU. The determination was performed on Venusil ASB C, with mo- bile phase consisted of acetonitrile-0.05% formic acid （22 ： 78） for Bes/5-FU, methanol-water （5 ： 95） for 5-FU at the flow rate of 1 ml/min. The detection wavelength was set at 262.7 nm for Bes/5-FU and 266 nm for 5-FU. The column temperature was 25 ℃, and sample size was 30 μl for Bes/5-FU and 20 μl for 5-FU. RESULTS： Bes/5-FU had been metabolized completely 2 h after medication. The was （0.14±0-04） h, MRT0-0h was （0.17 ±0-04） h, AUC0-10h was （17.73 ±6.27）μg·h/ml, AUC was （17.78 ±6.31） μg. h/ml for 5-FU. CONCLUSIONS： The method can detect plasma concentration of Bes/5-FU and its metabolite 5-FU in rats rapidly and accurately. Bes/5-FU is metabolized as 5-FU rapidly in vivo.

关 键 词：乌苯美司/5-氟尿嘧啶 高效液相色谱法 大鼠 药动学 

分 类 号：R965[医药卫生—药理学]