在体肠灌流模型研究灵仙新苷的大鼠肠吸收特性

目的:研究灵仙新苷在大鼠肠段的吸收特征。方法:以酚红为标示物,采用在体单向肠灌流模型,LC-MS/MS测定灵仙新苷在体肠灌流的浓度变化,研究灵仙新苷的吸收部位和吸收动力学特征。结果:灵仙新苷在大鼠小肠各肠段的吸收速率常数(Ka)、有效渗透系数(Peff)是十二指肠>空肠≈回肠,且十二指肠的Ka和Peff值与其他肠段存在显著性差异(P<0.05);灌流液中同一肠段不同浓度灵仙新苷的Ka和Peff均无统计学显著差异;盐酸维拉帕米和环孢素A均显著性降低对灵仙新苷的吸收(P<0.05)。结论:灵仙新苷在小肠有不同程度的吸收,其中在十二指肠吸收最好,药物浓度对灵仙新苷的Peff和Ka值无影响,其吸收机制为被动扩散,灵仙新苷可能不是P-糖蛋白底物。

Study on intestinal absorption of clematichinenoside AR in rats by in-situ single-pass perfusion model

Objective: To study the in-situ intestinal absorption behaviors of clematichinenoside AR(C-AR) in rats.Methods: The in-situ rat single-pass intestinal perfusion model was used,and the concentrations of the perfusate were determined by LC-MS/MS to investigate the intestinal absorption site and mechanism.Results: The absorption rate constants(Ka) and effective permeability values(Peff) of C-AR in three different region of rat intestine were in the following sequence: duodenum>jejunum≈ileum.The Ka and Peff of different drug concentration had no significant influence.The Ka and Peff of C-AR were significantly decreased by verapamil(P<0.05) and cyclosporine A(P<0.05).Conclusion: C-AR can be absorbed in the whole intestinal segment,and the best absorption site was duodenum.Its absorption mechanism may be related to passive diffusion.C-AR may not be the substrate of P-glyprotein.