天名精总倍半萜内酯在大鼠体内的药代动力学研究  

Pharmacokinetic study of total sesquiterpene lactone of Carpesium abrotanoides L in rats

作　　者：姚思凡 陈迪路 张艺 周小江[1,2] YAO Sifan;CHEN Dilu;ZHANG Yi;ZHOU Xiaojiang(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China;Hunan Provincial ResearchCenter for Standardization and Functional Engineering Technology of Decoction Pieces of TraditionalChinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南省中药饮片标准化及功能工程技术研究中心,湖南长沙410208

出　　处：《湖南中医药大学学报》2022年第8期1255-1260,共6页Journal of Hunan University of Chinese Medicine

基　　金：国家自然科学基金项目(31670362);湖南省自然科学基金项目(2020JJ4067);湖南省教育厅重点项目(19A368)。

摘　　要：目的建立测定大鼠血浆中3种天名精总倍半萜内酯[11(13)-二氢特勒内酯、特勒内酯、天名精内酯酮]含量的HPLC,探讨其在大鼠尾静脉给药后的药代动力学过程。方法从天名精中分离制备得到3种天名精总倍半萜内酯,通过尾静脉注射至健康雄性SD大鼠,剂量为50 mg·kg^(-1),给药后5、10、15、20、30、45 min及1、1.5、2、3、4、6、8 h通过眼底静脉丛取血。将采集的全血高速离心后吸取上层血浆,对天名精总倍半萜内酯进行药代动力学研究,计算相关药代动力学参数。结果天名精总倍半萜内酯3种成分单次尾静脉给药后,体内药代动力学过程中11(13)-二氢特勒内酯、特勒内酯符合三室模型,天名精内酯酮符合二室模型。11(13)-二氢特勒内酯、特勒内酯、天名精内酯酮血药质量浓度C_(max)分别为3.843、9.076、2.060μg/mL;曲线下面积AUC(0~T)分别为145.564、262.401、98.086 min/(μg·mL);药物半衰期t_(1/2)分别为15.835、62.318、41.843 min;血浆清除率CLz分别为0.183、0.145、0.311 L/(min·kg)。结论实验结果表明建立的HPLC方法快速、准确、灵敏,精密度、回收率均符合生物样品的测定要求,适用于11(13)-二氢特勒内酯、特勒内酯、天名精内酯酮3个成分在大鼠血浆中浓度的测定,11(13)-二氢特勒内酯、特勒内酯符合三室模型、天名精内酯酮符合二室模型。Objective To establish an HPLC for the determination of three total sesquiterpene lactone of Carpesium abrotanoides L[11(13)-dihydrotelekin,telekin and carabrone]in rat plasma and to investigate their pharmacokinetic processes after tail vein administration in rats.Methods Three total sesquiterpene lactone of Carpesium abrotanoides L were isolated and prepared from Carpesium abrotanoides L and injected into the tail vein of healthy male SD rats at a dose of 50 mg·kg^(-1),and blood was collected through the fundus venous plexus at 5,10,15,20,30,45 min and 1,1.5,2,3,4,6,8 h after administration.The whole blood collected was centrifuged at high speed and the upper plasma was aspirated to perform a pharmacokinetic study on the total sesquiterpene lactone of Carpesium abrotanoides L and calculate the relevant pharmacokinetic parameters.Results The in vivo pharmacokinetics of 11(13)-dihydrotelekin and telekin conformed to the three-compartment model,and that of carabrone conformed to the two-compartment model after a single tail vein administration of the three components of total sesquiterpene lactone of Carpesium abrotanoides L.The blood mass concentrations C_(max) of 11(13)-dihydrotelekin,telekin and carabrone were 3.843,9.076 and 2.060μg/mL,respectively;the area under the curve AUC(0~T)were 145.564,262.401 and 98.086 min/(μg·mL),respectively;the drug half-lives t_(1/2 )were 15.835,62.318 and 41.843 min,respectively;the plasma clearance CLz were 0.183,0.145 and 0.311 L/(min·kg),respectively.Conclusion The experimental results show that the established HPLC method is rapid,accurate,sensitive and precision and recovery rate are conform to the requirements of the determination of biological samples,suitable for the determination of the concentration of 11(13)-dihydrotelekin,telekin and carabron in rat plasma.11(13)-dihydrotelekin and telekin conformed to the three-compartment model,and that of carabrone conformed to the two-compartment.

关 键 词：天名精 天名精总倍半萜内酯 含量测定 药代动力学 HPLC 

分 类 号：R285.5[医药卫生—中药学]