吴茱萸粉末醋调敷日本大耳兔足心的药代动力学分析  

Pharmacokinetics of Euodiae Fructus Powder Dressing on Foot Sole of Japanese Big-ear Rabbits with Vinegar

作　　者：王森[1] 欧水平[2] 雷小娟[3] 

机构地区：[1]遵义医学院药学院,贵州遵义563003 [2]遵义医学院附属医院,贵州遵义563099 [3]南阳市第二人民医院,河南南阳473000

出　　处：《中国实验方剂学杂志》2017年第19期124-128,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：贵州省中医药管理局科研课题项目(ZYY2013-94);遵义医学院博士启动基金项目(遵医院办发[2013]69号)

摘　　要：目的:研究吴茱萸粉末醋调敷日本大耳兔足心后吴茱萸碱(EVO)和吴茱萸次碱(RUT)的药代动力学特征,探讨吴茱萸穴位贴敷疗法的药动学基础。方法:吴茱萸粉末(1.0 g·kg^(-1))醋调敷雄性日本大耳兔足心12 h,于不同时间点(0,1,2,3,4,5,6,8,10,12,24 h)心脏取血,血浆样品用乙腈萃取并沉淀蛋白,采用LC-MS检测血浆中EVO和RUT的血药浓度,采用Phenomenex Gemini C_(18)色谱柱(4.6 mm×150 mm,5μm),流动相乙腈-5 mmol·L^(-1)甲酸铵水溶液(62∶38),流速0.4 mL·min^(-1),柱温25℃,以色胺酮(TRY)为内标,采用电喷雾离子化(ESI)和正离子多离子反应监测(MRM)模式检测。采用PKSolver 2.0软件的非房室模型拟合药动学参数。结果:EVO和RUT的主要药动学参数半衰期(t_(1/2))分别为(18.55±7.98),(20.15±1.06)h;达峰时间(T_(max))分别为5,4 h;药峰浓度(C_(max))分别为(4.68±0.34),(9.76±1.05)μg·L^(-1);药时曲线下面积AUC_(0-t)分别为(58.18±5.46),(155.38±13.91)μg·L^(-1)·h,AUC_(0-∞)分别为(101.46±23.34),(300.32±36.22)μg·L^(-1)·h;平均驻留时间(MRT_(0-∞))分别为(27.63±9.34),(31.25±1.47)h。结论:吴茱萸粉末醋调敷日本大耳兔足心后,EVO和RUT均可透皮吸收入血,且撤药后24 h内仍能维持血药浓度,为吴茱萸穴位贴敷给药提供了实验依据。Objective： To study on the pharmacokinetic profiles of evodiamine （EVO） and rutaecarpine （RUT） from Euodiae Fructus powder dressing on the foot sole of Japanese big-ear rabbits with vinegar. Method： The Euodiae Fructus powder （1 g·kg^-1） was dressed on the foot sole of male Japanese big-ear rabbits with vinegar in 12 h,the blood was taken from the hearts at different time points （0,1,2,3,4,5,6,8,10,12,24 h） after administration.The plasma samples were pretreated by protein precipitation with acetonitrile,and the concentrations of EVO and RUT in rabbit whole blood were determined by LC-MS,taking Phenomenex Gemini C18 column （4.6 mm×150 mm,5 μm） with mobile phase of acetonitrile-5 mmol·L^-1 ammonium formate aqueous solution （62：38）,flow rate was 0.4 mL·min-1,column temperature was 25℃.Tryptanthrin （TRY） was adopted as the internal standard,electrospray ionization （ESI） was applied and operated in positive ionmode,quantification was performed by multiple reaction monitoring （MRM）.The main pharmacokinetic parameters were calculated by PKSolver 2.0 according to non-compartment model. Result： The t1/2 of EVO and RUT were（18.55±7.98）,（20.15±1.06） h,Tmax were 5,4 h,Cmax were （4.68±0.34）,（9.76±1.05） μg·L^-1,AUC0-t were （58.18±5.46）,（155.38±13.91） μg·L^-1·h,AUC0-∞ were （101.46±23.34）,（300.32±36.22） μg·L^-1·h,MRT0-∞ were （27.63±9.34）,（31.25±1.47） h. Conclusion： EVO and RUT can be absorbed into the blood through the skin of Japanese big-ear rabbits,and the drug concentration can be maintained within 24 h after withdrawal,which provides the experimental basis for point-application of Euodiae Fructus.

关 键 词：吴茱萸 吴茱萸碱 吴茱萸次碱 足心给药 药物代谢 色胺酮 

分 类 号：R969.1[医药卫生—药理学] R945[医药卫生—药学]