栀子-连翘药对大鼠体内药动学变化特征研究  

Changes of pharmacokinetics of Fructus Forsythiae-Fructus Gardeniae Herb Couple in rats

作　　者：孟祥乐[1,2,3,4] 李红伟[3] 韩永龙[1] 李颜[1] 万丽丽[1] 郭澄[1] 

机构地区：[1]上海交通大学附属第六人民医院药剂科,上海200233 [2]河南中医学院第一附属医院药学部,郑州450000 [3]河南中医学院,郑州450046 [4]济源市农业科学院,济源459002

出　　处：《中国新药杂志》2015年第17期2003-2009,2024,共8页Chinese Journal of New Drugs

基　　金：国家自然科学基金-河南联合基金(U1304824);河南省博士后基金资助(2014-75);河南中医学院第一附属医院博士科研基金(2012KJ30);河南中医学院博士科研基金(BSJJ2012-04)

摘　　要：目的:通过比较栀子-连翘药对配伍前后灌胃给药正常大鼠和发热模型大鼠体内主要化学成分连翘苷、栀子苷、连翘酯苷药动学参数的差异,阐述其配伍规律与作用机制。方法:将正常SD大鼠和发热模型大鼠随机分为栀子组、连翘组、栀子-连翘药对组。将栀子、连翘及药对水提物分别灌胃,中药提取物溶液为10 m L·kg-1(相当于单味药生药量3 g·kg-1),LC-MS-MS分析0,0.25,0.5,1,2,3,4,6,8,12,24 h血清样品。结果:正常SD大鼠与栀子组相比,配伍后栀子苷Cmax基本无变化,AUC0-t有升高趋势,但变化不显著(P>0.05);与连翘组相比,配伍后连翘苷Cmax和AUC0-t升高;与连翘组相比,配伍后连翘酯苷Cmax和AUC0-t降低,连翘苷与连翘酯苷的变化均没有显著差异(P>0.05)。大鼠采用背部皮下注射15%的干酵母悬液10m L·kg-1,建立大鼠发热模型,与连翘组相比,配伍后连翘苷Cmax和AUC0-t降低,连翘酯苷Cmax和AUC0-t变化不明显;与栀子组相比,配伍后栀子苷Cmax和均AUC0-t均增加,其中AUC0-t升高非常显著(P<0.01)。结论:正常SD大鼠栀子-连翘药对配伍前后对正常大鼠体内主要化学成分连翘苷、连翘酯苷和栀子苷的药动学特征影响不显著,配伍栀子对连翘苷、连翘酯苷的生物利用度仅有轻微影响。栀子-连翘药对配伍前后对发热模型大鼠体内主要化学成分连翘苷、连翘酯苷的药动学有一定影响,配伍栀子后连翘苷生物利用度显著降低、连翘酯苷的生物利用度增加不明显;栀子-连翘药对配伍后可显著提高发热模型大鼠体内主要化学成分栀子苷的血药浓度,增加栀子苷的生物利用度,可能是栀子-连翘药对配伍增效的作用机制之一。Objective： To Explore the law of composition and mechanism of action of Fructus ForsythiaeFructus Gardeniae herb couple by determining the content change of forsythin,geniposide and forsythiaside before and after composition. Methods： Normal and model SD rats were divided into Fructus Forsythiae,Fructus Gardeniae,and Fructus Forsythiae-Fructus Gardeniae herb couple groups and administered respectively with 10 m L·kg- 1of the freeze-dried powders dissolved in normal saline. Serum samples taken at 0,0. 25,0. 5,1,2,3,4,6,8,12 and 24 h were analyzed with LC-MS / MS. Results： Compared with Fructus Forsythiae,the Cmaxand AUC0- t of forsythin increased significantly after administration of Fructus Forsythiae-Fructus Gardeniae herb couple,whilethe maximum concentration and AUC0- tof forsythoside reduced without significant difference. The composition affected the pharmacokinetics of forsythin and forsythoside in model rats with fever. Compared with Fructus Gardenia,the Cmaxand AUC0- tof geniposide in the herb couple group significantly increased（ P〈0. 01）. Conclusion： The composition does not affect the pharmacokinetics of geniposide,forsythin and forsythoside significantly,but slight change of the bioavailability could be detected,which means the composition can increase the concentration of geniposide in blood and enhance its bioavailability,which may be one of the mechanisms of action of the herb couple.

关 键 词：药对 栀子 连翘 药物相互作用 药动学 配伍 

分 类 号：R978.7[医药卫生—药品]