白头翁皂苷B4在大鼠体内药代动力学规律及肺组织分布  

Pharmacokinetics and Lung Tissue Distribution of Anemoside B4 in Rats

作　　者：狄孟华 李桂凤 李言 崔京浩[2] 王永林[1] 杨世林[1] DI Menghua;LI Guifeng;LI Yan;CUI Jinghao;WANG Yonglin;YANG Shilin(Guizhou Medical University,Guiyang 550004,Guizhou,China;College of Pharmacy,Soochow University,Suzhou 215123,Jiangsu,China)

机构地区：[1]贵州医科大学,贵州贵阳550004 [2]苏州大学药学院,江苏苏州215123

出　　处：《贵州医科大学学报》2018年第7期745-749,共5页Journal of Guizhou Medical University

基　　金：国家自然科学基金项目资助(K113231513)

摘　　要：目的:建立用高效液相色谱(HPLC)法测定Wistar大鼠血浆及肺组织中白头翁皂苷B4(B4)的含量,研究其在大鼠体内的药代动力学规律及肺组织分布特征。方法:以气管滴注给予6 mg/kg的白头翁皂苷B4的大鼠作为气管滴注组,并与尾静脉给予6 mg/kg白头翁皂苷B4注射的大鼠作为尾静脉注射组,采用HPLC法于不同时间点(第5、15、30 min及1、2、4、6、8、10、12、14、24 h)的血药浓度,并于给药后5 min及1、2、4、8、12、24 h时测定测定气管滴注组大鼠肺组织中的B4浓度。结果:HPLC法测定血浆样品及肺组织样品中的内源性物质未对B4的检测结果形成干扰,B4在血浆及肺组织中的浓度分别在0.5~100.0 mg/L、0.5~400.0 mg/L范围与峰面积线性关系良好,最低定量限均为0.5 mg/L(S/N>10);室温下24 h的稳定性RE<11%,3次冻融稳定性RE<13%;白头翁皂苷B4在大鼠体内药动学过程符合二室模型;HPLC法测定结果表明,大鼠经气管滴注给药后,药物在肺中积蓄,且缓慢释放入血。结论:建立的HPLC法稳定可靠,肺部给予药物白头翁皂苷B4后,药物在肺中产生积蓄,缓慢入血,延长在体内的保留时间。Objective： To establish a HPLC method to determine anemoside B4 content in rat plasma and lung tissue,and study pharmacokinetics and distribution in lung tissue in rats. Methods： B4（ 6 mg/kg） was administered by intratracheal instillation and compared with the intravenous injection group with same quantity. Adopting HPLC method to determine plasma-drug concentration at different time point（ at 5,15,30 min and 1,2,4,6,8,10,12,14,24 h）; drug concentration was determined after intratracheal instillation of B4 in rat（ at 5 min after drug and 1,2,4,8,12,24 h）. Results： Endogenous substances in plasma sample and lung tissue samples did not interfere with the B4 test results;B4 showed good peak area linear relationship with the plasma and lung tissue with the concentration of0. 5 - 100. 0 mg/L and 0. 5 - 400. 0 mg/L,with low quantification limit of 0. 5 mg/L（ S/N 10）;24 h under room temperature showed stability RE 11%,three times freeze-thaw stability was RE 13%; the pharmacokinetics of B4 conformed to a two-compartment model after intratracheal instillation and intravenous injection. B4 was administered via tracheal instillation,drugs accumulated in the lungs and then slowly released to blood. Conclusions： Stable HPLC method was successfully developed. B4 was administered via tracheal instillation,drugs accumulate in the lungs,slowly enter the blood and prolong the retention time in the body.

关 键 词：药代动力学 高效液相色谱 白头翁皂苷B4 气管滴注 肺组织 血浆 

分 类 号：R285.5[医药卫生—中药学] O657.63[医药卫生—中医学]