小鼠非布司它的血药浓度和药代动力学测定  

Measurement of Plasma Concentration and Pharmacokinetic Parameters of Febuxostat in Mice

作　　者：李中皇[1] 熊莺[2] 万山河[1] 王广发[1] 张嘉杰[1] 

机构地区：[1]南方医科大学药学院,广东广州510515 [2]中山大学附属第一医院,广东广州510080

出　　处：《昆明医学院学报》2011年第8期19-22,共4页Journal of Kunming Medical College

基　　金：广州市粤港关键领域重点突破基金资助项目(2006Z1-E6021)

摘　　要：目的建立测定非布司它血浆药物浓度的液相色谱-质谱联用(LC-MS)分析方法,研究非布司它在小鼠体内的药代动力学.方法分别尾静脉(10 mg/kg)或口服(50 mg/kg)给予BALB/c小鼠非布司它,然后用LC—MS法测定血浆中非布司它浓度.用DAS软件计算非布司它的药代动力学参数,而绝对生物利用度(F)根据静注和口服的药时曲线下面积(AUC)之比来计算.结果非布司它在0.01～200 mg/L浓度范围内线性关系良好(r=0.9997,P<0.01),样品在血浆中的回收率大于85%,日内和日间RSD小于15%.小鼠静注10 mg/kg非布司它后药代动力学参数药时曲线下面积、半衰期、血浆分布容积、血浆清除率分别为:(62.91±4.68)mg/(L.h)、(12.35±1.06)h、(3.45±0.83)L/kg、(0.12±0.074)L/(h.kg);小鼠口服50 mg/kg非布司它后药代动力学参数药时曲线下面积、半衰期、达峰时间、峰浓度分别为(130.97±9.36)mg/(L.h)、(10.68±1.63)h、(1.5±0.11)h、(15.32±2.64)mg/L,在小鼠体内的绝对生物利用度为41.64%.结论用LC-MS联用方法测定的非布司它在小鼠体内血药浓度准确、可靠.非布司它药动力学参数详尽,为该药的临床研究提供了实验基础.Objective To establish a LC-MS method to measure the concentration of febuxostat in plasma and to investigate pharmacokinetic profile and absolute bioavailability of the drug in BALB/c mice.Methods Febuxostat was given intravenously to mice at 10 mg/kg or orally at 50 mg/kg,respectively.Blood samples were collected at various time following drug administration.Plasma concentration of febuxostat in mice was determined by LC-MS.Pharmacokinetics parameters were calculated by DAS software,and absolute bioavailability was assessed by the ratio of AUCp.o.to AUCi.v.Results The method was linear at the range of 0.01～200 mg/L（r =0.9997,P0.001）.The recovery of febuxostat in mice plasma was more than 85%.Intra-and inter-day precision,expressed as the relative standard deviation（RSD）was less than 15%.Area under the curve（AUC）,Half-life（T1/2）,volume of distribution（Vd）and plasma clearance（CL）for febuxostat（i.v.10mg/kg）in mice were（62.91±4.68）mg/（L.h）,（12.35±1.06）h,（3.45±0.83）L/kg,and（0.12±0.074）L/（h.kg）,respectively.On the other hand,AUC,T1/2,peak time（Tmax）and peak concentration（Cmax）for the drug（p.o.50 mg/kg）in mice were（130.97±9.36）mg/（L.h）,（10.68±1.63）h,（1.5±0.11）h and（15.32±2.64）mg/L,respectively.The absolute bioavailability of febuxostat in mice was 41.64%.Conclusion Pharmacokinetic parameters of febuxostat and the absolute bioavailability of febuxostat in mice determined by LC-MS are precise and reliable,and this provides an experimental basis for clinical study of the drug.

关 键 词：非布司它 液相色谱—质谱联用 药代动力学 生物利用度 

分 类 号：R965.1[医药卫生—药理学]