大鼠在体单向肠灌流模型研究冬凌草乙素的吸收动力学

Intestinal absorption properties of ponicidin by single pass perfusion model in rats

为测定冬凌草乙素在大鼠体内的吸收参数,研究冬凌草乙素的吸收动力学。采用高效液相色谱串联质谱法结合大鼠在体单向肠灌流吸收模型,从药物吸收部位、质量浓度和灌流介质等方面研究冬凌草乙素的各肠段吸收特征并计算吸收参数。结果在pH 6.5的灌流介质中冬凌草乙素较为稳定,肠道酶对其代谢影响较小,吸收显著高于pH 8.0碱性条件（P〈0.05）;不同质量浓度的冬凌草乙素在相同肠段吸收速率常数（Ka）、表观通透系数（Papp）无显著性差异,不同质量浓度的冬凌草乙素在大鼠十二指肠、空肠、结肠吸收速率常数（Ka）、表观通透系数（Papp）无显著性差异,但与回肠吸收参数具有显著性差异,均显著低于回肠吸收参数（P〈0.05）。盐酸维拉帕米对冬凌草乙素各肠段吸收均无显著性影响。结果表明10~1 000μg·L-1冬凌草乙素在大鼠全肠道均有吸收,其中回肠为最佳吸收部位,吸收特征为被动转运的线性动力学过程,无吸收饱和现象,弱酸性环境易于冬凌草乙素的肠道吸收,冬凌草乙素不是P糖蛋白的底物。

To determine the absorption properties and study the intestinal absorption kinetics of poncidin in rats. In situ single pass perfusion model was combined with High Performance Liquid Chromatography-Mass Spectrometry（HPLC-MS/MS） method to investigate the intestinal absorption characteristics and calculate absorption parameters with aspects of drug absorption,concentration and perfusion medium. The absorption of poncidin under acid condition at pH 6. 5 was more stable,where intestinal enzymes showed little influence on metabolism,and the absorption was significantly higher than that in pH alkaline condition at pH 8. 0（P〈0. 05）. Drug concentrations had no significant influence on absorption rate constant of the same intestinal segment Kaand apparent permeability coefficient Pappvalues of poncidin. Different concentrations of poncidin showed no significant differences in the Kaand Pappvalues among duodenum,jejunum and colon,but the values were significantly lower than ileum absorption parameters,with significant differences（P〈0. 05）. There was no significant effect of verapamil on intestinal absorption of poncidin. The results showed that poncidin could be absorbed at all the studied intestinal segments while ileum seemed to be the best absorption segment in the concentration range of 10-1 000 μg·L-1. The absorption was characterized by a linear dynamic process of passive transport,without absorption saturation. Weak acid environment was helpful for the intestinal absorption of poncidin,and ponicidin was not a substrate of P-glycoprotein（P-gp）.