冬凌草滴丸大鼠体内药动学研究  

In vivo Pharmacokinetics Study on Donglingcao Dropping Pills in Rats

作　　者：谢涛 杨婷 郑大勇 李伟 于德红 韩倩[2] XIE Tao;YANG Ting;ZHENG Dayong;LI Wei;YU Dehong;HAN Qian(School of Pharmacy,North China University of Science and Technology,Tangshan 063210,China;Department of Radiotherapy,Henan Provincial People's Hospital,Zhengzhou 450003,China)

机构地区：[1]华北理工大学药学院,唐山063210 [2]河南省人民医院放疗科,郑州450003

出　　处：《医药导报》2022年第4期429-437,共9页Herald of Medicine

基　　金：华北理工大学博士科研基金项目(28418499)。

摘　　要：目的建立在大鼠血浆中同时测定冬凌草甲素与冬凌草乙素的高效液相色谱-串联质谱法(LC-MS/MS),研究不同给药剂量冬凌草滴丸中冬凌草甲素与冬凌草乙素在大鼠体内的药动学特征。方法冬凌草滴丸以小(0.3 g·kg^(-1))、中(0.9 g·kg^(-1))、大(2.7 g·kg^(-1))剂量以及累积剂量(0.9 g·kg^(-1),连续给药7 d)对大鼠灌胃给药,以苯海拉明作为内标物,采用LC-MS/MS分析方法检测血浆中冬凌草甲素、冬凌草乙素的浓度,绘制药物浓度-时间曲线。采用DAS3.0版软件计算药动学参数。结果冬凌草滴丸以小、中、大剂量给药后,冬凌草甲素的峰浓度(C_(max))分别为(74.25±29.93),(197.67±38.09),(346.03±34.87)ng·mL^(-1),药物浓度-时间曲线下面积(AUC_(0-t))分别为(85.46±36.06),(187.21±44.27),(654.66±88.50)ng·mL^(-1)·h;冬凌草乙素的C_(max)分别为(30.33±16.15),(37.88±11.95),(60.92±36.60)ng·mL^(-1),AUC_(0-t)分别为(17.44±4.16),(70.77±33.31),(136.25±3.65)ng·mL^(-1)·h。冬凌草滴丸中剂量单次给药与中剂量多次给药后,冬凌草甲素消除半衰期(t_(1/2β))分别为(2.24±1.17),(2.85±0.82)h,冬凌草乙素t_(1/2β)分别为(2.56±0.45),(2.73±0.62)h。结论大鼠给予冬凌草滴丸小、中、大剂量给药后,冬凌草甲素AUC_(0-t)呈线性动力学特征,中剂量单次给药与多次给药后,体内均无蓄积。Objective To establish a LC-MS/MS method for the simultaneous determination of oridonin and ponicidin in rat plasma,and to study the pharmacokinetic characteristics of oridonin and ponicidin at different doses of donglingcao dropping pills.Methods Different doses of donglingcao dropping pills were administrated at low(0.3 g·kg^(-1)),medium(0.9 g·kg^(-1)),high(2.7 g·kg^(-1)),and cumulative dosage(25 mg·kg^(-1),7days),respectively.Diphenhydramine was chosen as the internal standard,and LC-MS/MS was used to determine the concentrations of oridonin and ponicidin in rat plasma.Then concentration-time curves were obtained.Pharmacokinetic parameters were calculated by DAS 3.0 software.Results After the administration of the pills at low,medium and high doses,the peak concentrations(C_(max))of oronidin at doses of 0.3,0.9,and 2.7 g·kg^(-1) were(74.25±29.93),(197.67±38.09),and(346.03±34.87)ng·mL^(-1),respectively.The AUC_(0-ts) were(85.46±36.06),(187.21±44.27),and(654.66±88.50)ng·mL^(-1)·h,respectively.The C_(maxs) of ponicidin at doses of 0.3,0.9,and 2.7 g·kg^(-1) were(30.33±16.15),(37.88±11.95),and(60.92±36.60)ng·mL^(-1),respectively.The AUC_(0-ts) were(17.44±4.16),(70.77±33.31),and(136.25±3.65)ng·mL^(-1)·h,respectively.The elimination half-life(t1/2β)of oronidin at single dose and multiple doses of 0.9 g·kg^(-1) were(2.24±1.17)and(2.85±0.82)h,respectively.The t_(1/2β) of ponicidin at a single dose and multiple doses of 0.9 g·kg^(-1) were(2.56±0.45)h and(2.73±0.62)h,respectively.Conclusion After low(0.3 g·kg^(-1)),medium(0.9 g·kg^(-1)),and high(2.7 g·kg^(-1))doses of donglingcao dropping pills were administrated,the AUC_(0-t) of oridonin showed linear dynamic characteristics,and there was no accumulation in the body at the medium dose of single and multiple doses administration.

关 键 词：冬凌草滴丸 冬凌草甲素 冬凌草乙素 高效液相色谱-串联质谱法 药动学 

分 类 号：R973[医药卫生—药品]