基于在体单向肠灌流法探究刺囊酸的大鼠肠吸收特性  

Investigation of intestinal absorption of echinocystic acid by single pass intestinal perfusion model in rats

作　　者：刘婉霞 陈瑞 班玉娟 汤磊 黄家宇 LIU Wan-xia;CHEN Rui;BAN Yu-juan;TANG Lei;HUANG Jia-yu(School of Pharmacy,Guizhou Medical University,Guiyang 550004,China;Engineering Technology Research Center for Research and Utilization of Chemical Synthetic Drugs of Guizhou Province,Guiyang 550004,China)

机构地区：[1]贵州医科大学药学院,贵阳550004 [2]贵州省化学合成药物研发利用工程技术研究中心,贵阳550004

出　　处：《中国新药杂志》2022年第10期998-1002,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(81660573)。

摘　　要：目的:考察刺囊酸在小肠不同肠段、不同条件下的吸收特性,探究刺囊酸的吸收机制。方法:采用大鼠单向肠灌流模型,考察不同浓度药物、不同肠段、不同p H条件以及P-糖蛋白(P-gp)抑制剂对刺囊酸吸收的影响,利用HPLC法测定药物浓度。结果:刺囊酸在十二指肠的吸收随浓度增加而增加,相同浓度下,各肠段间的有效渗透系数(Peff)和吸收速率常数(Ka)无显著性差异(P> 0.05),在小肠各段吸收均较好,不同pH条件下结果表明,刺囊酸在碱性条件下吸收较好。与P-gp抑制剂组相比吸收无显著性差异(P>0.05)。结论:刺囊酸在小肠全段均有吸收,且吸收完全,其吸收速率最快的部位是回肠;低浓度与中高浓度组间有显著差异,推测刺囊酸的吸收机制不是简单的被动转运;根据生物药剂学分类系统初步判定刺囊酸为Ⅱ类低溶解性/高渗透性药物。刺囊酸不是P-gp的底物,本实验初步探明刺囊酸的吸收特性,可为药物制剂及临床研究提供生物学依据。Objective: To investigate the absorption characteristics of echinocystic acid in different segments of the small intestine under different conditions. Methods: The rat single pass intestinal perfusion model was used to study the effects of different drug concentrations,different intestinal segments,pH values and P-glycoprotein inhibitors on the absorption of echinocystic acid. The drug concentration was determined by HPLC. Results: The absorption of echinocystic acid in duodenum increased with the increase of concentration. The test at different pH values showed that the absorption was better in alkaline conditions. There was no significant difference in drug absorption compared with that of the P-gp inhibitor group( P > 0. 05). Conclusion: Echinocystic acid is absorbed in the entire small intestine,and the absorption is complete. The drug has the fastest absorption rate in the ileum.There is significant difference in the absorption between the low-concentration and medium-high-concentration groups. It is speculated that the absorption mechanism of echinocystic acid is not simple passive transport. According to the BCS echinocystic acid is determined as a class Ⅱ low-solubility/high-permeability drug. Echinocystic acid is not a substrate of P-gp. This experiment has preliminarily proved the absorption characteristics of echinocystic acid,which can provide biological basis for the development of pharmaceutical preparations and clinical research.

关 键 词：刺囊酸 单向肠灌流法 肠吸收特性 五环三萜 高效液相色谱 

分 类 号：R965.2[医药卫生—药理学]