在体肠灌流模型研究灵仙新苷的大鼠肠吸收特性

摘要

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.%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 (K,) and effective permeability values (Peff) of C-AR in three different region of rat intestine were in the following sequence: duodenum > jejunum = ileum. The Kt and Peff of different drug concentration had no significant influence. The Kt 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.