桂枝汤类方主要成分在大鼠体内药代动力学比较研究  

Pharmacokinetics of Guizhi Decoctions in rats

作　　者：陈莹蓉[1] 高成璐[2] 裘福荣[2] 马越鸣[1] 

机构地区：[1]上海中医药大学中药学院药理学教研室,上海201203 [2]上海中医药大学附属曙光医院临床药代动力学实验室,上海201203

出　　处：《中成药》2013年第4期683-689,共7页Chinese Traditional Patent Medicine

基　　金：上海高校创新团队建设项目(2009);上海市教委重点学科建设项目(J50303);重大新药创制项目(2012ZX09303009-001)

摘　　要：目的比较桂枝汤类方不同配伍大鼠体内的药动学差异。方法 LC-MS/MS法分析大鼠灌服桂枝汤、桂枝加桂汤和桂枝加芍药汤后在大鼠体内的桂皮酸、马尿酸、芍药苷和甘草次酸血药浓度和药动学参数的差异,以及配伍对芍药苷肠菌代谢的影响。结果大鼠灌服桂枝汤类方血浆中桂皮酸、马尿酸及甘草次酸的药动学参数经剂量校正后差异均无统计学意义。但桂枝加芍药汤中芍药苷的Cmax升高(P<0.05)。大鼠灌胃芍药苷后其AUC和Cmax与给药剂量呈线性关系。配伍甘草对芍药苷肠菌代谢的抑制作用最强。结论桂枝汤类方的不同配伍对芍药苷在大鼠体内的药动学有影响,其机理可能是抑制了芍药苷的肠菌代谢。AIM To compare the differences of pharmacokinetics among Guizhi Decoctions.METHODS LC-MS/MS was employed to analyze the plasma concentrations of cinnamic acid,hippuric acid,peoniflorin and glycyrrhetic acid in rats fed with Guizhi Decoction（Cinnamomi Ramulus,Paeoniae alba Radix,Glycyrrhizae Radix et Rhizoma,Zingiberis recens Rhizoma,Jujubae Fructus）,Guizhi Decoction plus Cinnamomi Ramulus and Guizhi Decoction plus Paeoniae Radix,respectively.The differences of pharmacokinetic parameters and the effect of peoniflorin on the intestinal flora metabolism were tested.RESULTS After dose correction,the pharmacokinetic parameters of cinnamic acid,hippuric acid and glycyrrhetinic acid showed no significant difference on Guizhi Decoctions,but paeoniflorin content in Guizhi Decoction plus Paeoniae Radix increased and showed a statistical difference with a dose-dependent relationship.The inhibitory effect of adding Glycyrrhizae Radix et Rhizoma on paeonifiorin metabolism presents the most in relation to the inhibition of intestinal flora metabolism.CONCLUSION Pharmacokinetics of peoniflorin were different among Guizhi Decoctions in rats.The inhibition of compatibility on the metabolism of paeoniflorin by intestinal flora contributed to the pharmacokinetic difference of paeoniflorin.

关 键 词：桂枝汤类方 LC-MS MS 药代动力学 配伍 芍药苷 肠菌代谢 

分 类 号：R969.1[医药卫生—药理学]