毛蕊花糖苷在大鼠体内吸收、分布及排泄研究  

Absorption,distribution and excretion of acteoside in rats

作　　者：霍仕霞 李建梅 高莉 彭晓明 陈西敬[2] 文彦丽[2] 闫明 

机构地区：[1]新疆维吾尔自治区维吾尔医药研究所,新疆维吾尔医方剂学实验室,新疆乌鲁木齐830049 [2]中国药科大学药物代谢与动力学研究中心,江苏南京211198

出　　处：《中国医院药学杂志》2016年第6期450-454,共5页Chinese Journal of Hospital Pharmacy

基　　金：新疆维吾尔自治区科研机构创新发展专项资金(编号:2014003)

摘　　要：目的:采用液相色谱-质谱联用(LC-MS/MS)法测定大鼠血浆及组织样品中毛蕊花糖苷的浓度,并探讨其在大鼠体内吸收、分布及排泄研究。方法:SD大鼠灌胃给予毛蕊花糖苷20,40,80,160 mg·kg^(-1)后,于不同时间点采血,给予40 mg·kg^(-1)剂量进行分布和排泄试验,测定血浆、组织和排泄物中的毛蕊花糖苷浓度,并用DAS 2.0软件拟合并计算药动学参数。结果:大鼠给药20,40,80,160 mg·kg-1的毛蕊花糖苷后,药时曲线呈二室开放模型,主要药动学参数tmax,Cmax,t1/2α,AUC0-t,AUC0-∞,CL/F,V/F分别为(17.50±10.37)min、(0.313±0.04)mg·L-1、(6.79±12.10)min、(21.39±4.03)mg·L^(-1)·min^(-1)、(22.39±3.89)mg·L^(-1)·min^(-1)、(1.83±0.30)L·min^(-1)·kg-1、(179.10±52.77)L·kg^(-1)。大鼠给予40 mg·kg-1的毛蕊花糖苷后,毛蕊花糖苷在尿液和粪便中36 h内的累积排泄百分数分别为(0.037±0.005)%、(0.004 2±0.000 8)%,胆汁中12 h内的累积排泄率基本为零。结论:毛蕊花糖苷在大鼠体内吸收符合一级动力学,分布在小肠和肺浓度最高,其次为胃和肌肉,其他组织都有少量的分布;且通过尿液、粪便和胆汁排泄量较少,其可能主要通过代谢过程进行消除。OBJECTIVE To establish a LC-MS/MS method for determination of acteoside in plasma and tissues of rats and investigate absorption,distribution and excretion of acteoside in rats.METHODS SD rats were given20,40,80 and 160 mg·kg^-1 acteoside ig.Blood samples were collected at different times after oral administration.Concentrations of acteoside in plasma,tissues and excretion were determined by LC-MS/MS,and pharmacokinetics were calculated by DAS 2.0software.RESULTS After administration of acteoside,concentration-time curve of acteoside was best fitted to a two compartment open model.Main pharmacokinetie parameters tmax,Cmax,t1/2,AUC0-t,AUC0-∞,CL/Fand V/F were respectively（17.50±10.37）min,（0.313±0.04）mg·L^-1,（6.79±12.10）min,（21.39±4.03）mg·L^-1·min^-1,（22.39±3.89）mg·L^-1·min^-1,（1.83±0.30）L·min～（-1）·kg^-1 and（179.10±52.77）L·kg^-1.After administration of 40 mg·kg^-1 acteoside,percentage of cumulative excretion were（0.037±0.005）%and（0.004 2±0.000 8）%,respectively in urine and fecal matter of rats thirty six hours later,but zero in bile twelve hours later.CONCLUSION The characters of acteoside are first-order kinetics,intestine and lung are major distribution organs,stomach and muscle rank the second.There are very few acteoside excreted through urine,fecal matter or bile.The major way of elimination is metabolism.

关 键 词：毛蕊花糖苷 液相色谱-质谱联用法 大鼠 吸收 分布 排泄 

分 类 号：R969[医药卫生—药理学]