马钱苷肠吸收机制的研究  

Studies on absorption mechanism of loganin in intestines of rats

作　　者：李文兰[1] 扈正婷[1] 季宇彬[1] 王晓冬[1] 徐栋[1] 

机构地区：[1]哈尔滨商业大学生命科学与环境科学研究中心

出　　处：《中国中药杂志》2008年第9期1052-1055,共4页China Journal of Chinese Materia Medica

基　　金：黑龙江省科技厅攻关项目(GC05C31601);黑龙江省教育厅振兴老工业基地项目(1151gzd25)

摘　　要：目的：考察药物浓度、肠段、pH及P-gP对马钱苷肠吸收机制的影响规律。方法：将大鼠分为10组：马钱苷高、中、低剂量组（0．1，o．025，0．0125mg·mL^-1）；十二指肠、空肠及回肠组（0．013mg·mL^-1）；pH6，7，8组（0．013mg·mL^-1）；诱导剂利福平组（0．0125mg·mL^-1）。采用大鼠在体循环灌流法，应用HPLC测定肠吸收循环液中马钱苷的浓度，UV法测定肠吸收循环液中即时酚红浓度。结果：马钱苷在0．0125—0．1mg·mL^-1，其吸收量与药物浓度呈线性关系，且各浓度吸收速率基本不变；pH对马钱苷吸收没有显著影响；各个肠段的吸收速率及吸收量顺序为回肠〉十二指肠〉空肠；此外，P-gp诱导剂利福平对马钱苷的吸收有明显的抑制作用。结论：马钱苷在肠道的吸收呈一级动力学过程，吸收机制推断为被动扩散；具有特定的吸收部位，宜制成胃肠道滞留型定位释药系统；马钱苷为P-gp底物，可以通过与P—gp抑制剂合用提高其生物利用度。Objective： To investigate the absorption mechanism of loganin at different intestine segments of rats and the influence of the drug solution concentration, pH, P-gp inductor. Method： Rats were randomly divided into 10 groups, high, middle and low concentration groups（0.1,0. 025,0. 012 5 mg · mL^-1 ）, duodenum, jejunum and ileum groups（0. 013 mg · mL^-1 ）, high, middle and low pH groups（0. 013 mg· mL^-1 ）, inducer group（0. 013 mg· mL^-1 ）. The intestine cannulation was performed for in situ recirculation. Loganin concentration in the flux was measured by the reversed phase HPLC. Result： When the concentration was raised from 0. 012 5 to 0.1 mg· mL^-1 , the uptake of loganin was linearly increased, and no change of Ka is not found. The pH of flux has no effect on drug absorption. The absorbed dose and Ka sequence （from high to low） of loganin at different intestine segments is ileum, duodenum, jejunum. Furthermore, P-gp inductor RFP has effect on the intestinal absorption. Conclusion： The absorption of loganin in intestine of rat is a first-order kinetics, the absorption mechanism is probably the passive diffusion. It has specific absorption locus and access to locating administration, meanwhile it＇s the P-gp substrate, and could increase its fraction of bioavailability by corporation with P-gp inhibitor.

关 键 词：马钱苷 吸收机制 HPLC 

分 类 号：R285.5[医药卫生—中药学]