基于大鼠原位肠-肝血管灌流模型研究甘草酸的代谢  

Metabolism of glycyrrhizin and glycyrrhetinic acid in the in situ vascularly perfused rat intestine-liver model

作　　者：钟运鸣[1,2] 王素军[1,2] 曾洁[1,2] 黄丽花[1,2] 程漩格 王桂香[2] 臧林泉[2] 

机构地区：[1]广东药学院临床药学系,广东广州510006 [2]广东药学院药科学院药理系,广东广州510006

出　　处：《中国药理学通报》2014年第4期501-505,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81073141);2010年科技部新药重大专项资助项目(No 2011zx09102-001-31);广东省"十二五"医学重点学科资助项目(依托广东药学院附属第一医院;药科学院)

摘　　要：目的研究甘草酸在大鼠体内的肠、肝中的生物转化。方法建立大鼠原位肠-肝血管灌流模型,采用LC-MS/MS方法测定灌流液中的甘草酸和甘草次酸。结果甘草酸在单向肠-肝血管灌流模型中稳态肠提取率和稳态肝提取率分别为(4.2±0.6)%和(28.0±3.0)%,灌流液中未发现代谢物甘草次酸;原位循环肠血管灌流模型中甘草酸的一级吸收速率常数为(0.33±0.06)min-1;甘草酸在大鼠十二指肠给药后,灌流液中主要活性代谢产物为甘草次酸,同时肠腔液也存在大量甘草次酸。结论甘草酸的首过效应明显,口服后其主要被肠道菌群或肝细胞代谢,在肠粘膜细胞仅少量代谢。大鼠原位肠-肝血管灌流模型适用于甘草酸的药动学研究。Aim To study the biotransformation of gly-cyrrhizin in rat intestine-liver. Methods The in situ vascularly perfused rat intestine-liver model was estab-lished with a validated LC-MS/MS method for assay of the model perfusate glycyrrhizin and glycyrrhetinic acid. Results The steady state intestinal and liver ex-traction ratios in the once-through perfused rat intes-tine-liver model for glycyrrhizin were （ 4. 2 ＆#177; 0. 6 ）%and （28. 0 ＆#177; 3. 0）%, respectively; the first-order ab-sorption rate constant for glycyrrhizin in the recircula-tion of perfusate to the intestine model was （ 0. 33 ＆#177; 0. 06 ） min-1;after intraduodenal administration of gly-cyrrhizin,the main active metabolite in was the perfu-sate glycyrrhetinic acid, which was also found in intes-tinal luminal fluids. Conclusions The first-pass effi-cacy of glycyrrhizin is obvious and there is only a small amount of metabolite in the intestinal mucosa cells;gly-cyrrhizin is metabolized by gut bacteria or liver cells af-ter oral administration;the in situ vascularly perfused rat intestine-liver model can be used in glycyrrhizin pharmacokinetic studies.

关 键 词：甘草酸 甘草次酸 原位肠-肝血管灌流模型 代谢 大鼠 药动学 

分 类 号：R332[医药卫生—人体生理学] R284.1[医药卫生—基础医学]