钩吻素子在大鼠体内的药物代谢动力学及组织分布  

Pharmacokinetics and Tissue Distribution of Koumine in Rats

作　　者：许盈[1] 郑宓[1] 李苏平[1] 苏燕评[1] 杨渐[1] 刘铭[1] 俞昌喜[1] 

机构地区：[1]福建医科大学药学院药理学系,福州350004

出　　处：《福建医科大学学报》2013年第4期199-203,共5页Journal of Fujian Medical University

基　　金：国家自然科学基金面上项目(81273493);福建省科技厅社会发展重点项目(2009Y0026);福建省改革与发展委员会产业技术开发项目(闽发改投资[2009]958号);福建医科大学重大科研项目(09ZD009)

摘　　要：目的建立HPLC测定大鼠血液和组织钩吻素子含量的方法,进而研究单次灌胃给予钩吻素子的大鼠体内药动学以及组织分布。方法采用萃取法预处理大鼠的血液和组织样品;建立HPLC-紫外检测法测定生物样品的钩吻素子含量。大鼠单次灌胃给予钩吻素子15mg/kg后,于不同时间点收集血液和组织样本,HPLC法测定大鼠血浆和组织中的钩吻素子含量,计算药代动力学参数。结果建立的HPLC测定血液和组织钩吻素子含量的方法,专属性好,线性范围分别为0.06～10.00μg/mL和0.08～5.00μg/mL,日内和日间RSD均<9%,提取回收率分别为80.03%～83.55%和64.20%～76.82%,方法回收率分别为99.21%～110.36%和91.87%～109.25%。雄性SD大鼠单次灌胃给予15mg/kg钩吻素子,达峰时间为(19.95±0.53)min,消除半衰期为(234.11±17.37)min,表观分布容积为(10.45±0.36)L/kg,曲线下面积为(142.35±5.86)mg·min·L-1。给药5min后,待检组织均检出钩吻素子,且多数组织浓度已达峰,组织浓度在胃、体脂、肝、肾、脾、小肠较高;随后,多数组织中的药物含量随时间推移而下降,但肝脏和小肠含量在给药后15min最高;给药60min后多数组织药物含量较低,其中骨骼肌和睾丸已低于检测限。结论本HPLC测定生物样品钩吻素子含量的方法操作简便,准确灵敏,可用于钩吻素子体内药动学研究;钩吻素子在大鼠体内的药代动力学符合二室模型;钩吻素子在大鼠体内分布迅速广泛,以消化道浓度为高,可透过血脑屏障,消除速度快。Objective To develop high performance liquid chromatography （HPLC） methods for the determination of Koumine in rat plasma and tissues, and to further determine the pharmacokinetics and tissue distribution in rats with a single intragastric administration of Koumine. Methods An extraction method was employed as the sample preparation technique. HPLC-ultraviolet methods were developed to determinate the concentration of Koumine in biological samples. Rats were intragastricly administered asingle dose of 15 mg/kg Koumine. Blood and tissue samples were collected at different time points. The concentrations of Koumine in plasma and tissues were determined by the established HPLC method and the pharmacokinetic parameters were calculated. Results The established HPLC methods have good specificities, and the linear range was between 0.06~10.00/ag/mL for blood sample and 0.08-5.00μg/mL for tissue sample. Both the intra- and inter-day precisions were less than 9 %. The ranges of extraction re- covery were 80.03%-83.55% and 64.20%-76.82% respectively. The ranges of method recovery were 99.21%--110.36% and 91.87%--109.25% respectively. The peak time was （19. 95±0. 53）min,the elimination half life （234.11±17.37） rain, the apparent volume of distribution （10.45--t- 0.36） L/kg, the area under curve （142.35±5.86）mg . min· L-1 after male SD rats were administered intragastricly with a single 15 mg/kg Koumine. Koumine was found in all the examined tissues 5 min post dosing at which time the Koumine concentrations reached peak in most of these tissues, particulary in stomach, body fat, liver, kidney, spleen and intestine. The concentrations of Koumine in most tissues were declined with time. However, the concentrations of Koumine in liver and intestine peaked 15 min after dosing. Sixty minutes after dosing, the concentrations of Koumine were low in tissues, even undetectable in muscles and testis. Conclusions The method is simple, accurate and sensitive that can be used to determine the phar- macokinetics o

关 键 词：钩吻 钩吻碱 钩吻素子 药代动力学 组织分布 色谱法 高压液相 

分 类 号：R96[医药卫生—药理学]