连翘酯苷A在大鼠体内的药动学及其血浆蛋白结合率研究  

Investigation of pharmacokinetics and plasma protein binding of forsythiaside A in rats

作　　者：程凌飞[1] 褚扬[2] 胡晨旭[2] 郭嘉华[2] 万梅绪[2] 周水平[2] 郭治昕[1,2] 闫希军[1,2] 

机构地区：[1]天津中医药大学,天津300193 [2]天津天士力研究院,天津300410

出　　处：《中国新药杂志》2010年第23期2138-2141,2160,共5页Chinese Journal of New Drugs

基　　金：国家重大新药创制科技重大专项(2008ZX09401-006)

摘　　要：目的:研究连翘酯苷A在大鼠体内的药动学及其血浆蛋白结合率。方法:大鼠按10 mg.kg-1静脉注射连翘酯苷A,不同时间点采集血样。采用高效液相色谱法(HPLC)测定其血药浓度,应用Topfit 2.0软件计算其主要药动学参数;采用超滤法研究连翘酯苷A的血浆蛋白结合率。结果:大鼠静脉注射连翘酯苷A后主要药动学参数为t1/2=(20.6±4.4)min,Ke=(0.034±0.006)min-1,Vd=(0.66±0.14)L,CL=(22.2±1.7)mL.min-1,MRT=(5.29±1.12)min,AUC0～100 min=(450.97±36.04)μg.min.mL-1,AUC0～∞=(453.22±36.37)μg.min.mL-1。连翘酯苷A在浓度为1,5和25μg.mL-1时,大鼠平均血浆蛋白结合率分别为69.3%,67.2%和62.9%。结论:连翘酯苷A在大鼠体内符合二室开放模型,具有体内分布快、血药浓度下降迅速等特点。同时,血浆蛋白结合率结果表明,连翘酯苷A具有中等强度的血浆蛋白结合率。Objective： To investigate the pharmacokinetics and plasma protein binding of forsythiaside A in rats.Methods： Rat blood samples were collected at a series of time points after intravenous administration of 10mg·kg^-1 forsythiaside A.Then the forsythiaside A concentrations were determined by HPLC,and the main pharmacokinetic parameters were calculated using Topfit 2.0 pharmacokinetic software.An ultrafiltration method was employed to determine plasma protein binding of forsythiaside A.Results： After intravenous administration of forsythiaside A,the pharmacokinetic parameters were as follows： t1/2=（20.6±4.4）min;Ke=（0.034±0.006）min^-1;Vd=（0.66±0.14）L;CL=（22.2±1.7）mL·min^-1;MRT=（5.29±1.12）min;AUC0～100 min=（450.97±36.04）μg·min·mL^-1;AUC0～∞=（453.22±36.37）μg·min·mL^-1.The average plasma protein binding of forsythiaside A was 69.3%,67.2% and 62.9% at the concentrations of 1,5 and 25μg·mL^-1,respectively.Conclusion： The pharmacokinetics of forsythiaside A fits to two-compartment model,and shows a rapid distribution and a quick elimination process in rats.Forsythiaside A has a moderate binding capacity to plasma protein.

关 键 词：连翘酯苷A 药动学 血浆蛋白结合率 高效液相色谱法 超滤法 

分 类 号：R969.1[医药卫生—药理学]