基于在体单向肠灌流模型探究去氢骆驼蓬碱衍生物HM-Y-A的肠吸收特性

Intestinal absorption of harmine derivative HM-Y-A by in situ single pass intestinal perfusion model in rats

目的考察去氢骆驼蓬碱衍生物(HM-Y-A)在小肠不同肠段、不同条件下的吸收特性,探究HM-Y-A的吸收机制。方法采用大鼠在体单向肠灌流模型结合HPLC测定法,考察不同肠段、不同药物浓度、不同pH值及P-糖蛋白抑制剂对HM-Y-A吸收参数(K_(a)和P_(app))的影响。结果HM-Y-A在小肠各段均有吸收,最佳吸收肠段是十二指肠和空肠;随着药物浓度升高,吸收参数K_(a)和P_(app)不断降低,低浓度与中、高浓度间差异具有统计学意义(P<0.05);在pH 6.4和7.4时K_(a)和P_(app)显著增高(P<0.05);加入P-糖蛋白抑制剂前后,吸收参数差异无统计学意义。结论HM-Y-A在小肠全段均有吸收,在十二指肠和空肠吸收较好;吸收机制可能以主动吸收或促进扩散为主;药物在偏碱性条件下吸收较好;HM-Y-A可能不是P-gp的底物。

Objective To determine the absorption characteristics of harmine derivative HM-Y-A in different intestinal segments and under different conditions.Methods The rat single pass intestinal perfusion model combined with HPLC assay was used to determine the effect of different intestinal segments,different drug concentrations,pH values and P-glycoprotein(P-gp)inhibitors on the absorption of HM-Y-A.Results HM-Y-A was absorbed in the entire intestine,with the best absorption in the duodenum and the jejunum.With the increase of drug concentration,the absorption parameters K_(a) and P_(app) decreased continuously,with a significant difference between low concentration and medium and high concentration(P<0.05).K_(a) and P_(app) increased significantly at pH 6.4 and 7.4(P<0.05).There was no significant difference in the absorption parameters before and after adding the inhibitor.Conclusion HM-Y-A is absorbed in all intestinal segments,and better absorbed in the duodenum and the jejunum.The absorption mechanism may be active absorption or promotion of diffusion with better absorption in the alkaline conditions.HM-Y-A may not be a substrate for P-gp.