在体低速单向灌流模型考察Hup-A的肠吸收部位

Study on Intestinal Absorption Parts of Huperize A by in situ Low- speed Single Pass Perfusion Model

目的：研究石杉碱甲（Hup-A）大鼠在体肠吸收部位。方法：运用大鼠在体低速单向肠灌流模型,以酚红为标示物,分别研究了不同浓度及不同肠段Hup-A的吸收情况。通过肠腔有效吸收系数（Peff）、吸收速率常数（Ka）和药物吸收剂量分数（fa）评价药物的吸收部位,考察Hup-A的吸收动力学。结果：Hup-A在0.5-10.0μg·m L^-1浓度内,药物累积吸收量随着灌流液药物浓度的增加而提高,Hup-A的吸收曲线近似线性状态,无浓度抑制作用,且不同浓度Hup-A的Peff,Ka,fa均无显著性差异（P〉0.05）。当灌流液浓度为10μg·m L^-1时,Hup-A在大鼠各肠段的Peff、Ka和fa依次为十二指肠〉回肠〉空肠〉结肠,且结肠与其他肠段均有显著性差异（P〈0.05）,其Peff值分别为（0.57±0.04）×10^-4cm^-1·s^-1,（0.53±0.02）×10^-4cm^-1·s^-1,（0.48±0.05）×10^-4cm^-1·s^-1,（0.41±0.06）×10^-4cm^-1·s^-1。结论：Hup-A在大鼠各肠段均有不同程度的吸收,药物浓度对Hup-A的肠吸收无影响。因此,其在肠道的吸收呈现一级吸收动力学,吸收机制为被动扩散。

Objective： To investigate the Huperize A absorption in parts of rats intestine. Method： After low- speed single pass perfusion model of rats in situ was set up,by takingphenolsulfonphthalein as a marker,the absorption kinetics of Huperize A in small intestine was explored under conditions of differentconcentrationsand segments. The drugabsorption was evaluated by effective permeability（ Peff）,absorption rate constant（ Ka） and fraction absorbed（ fa）. Results： With the increase of Huperize A＇s concentration range of 0. 5- 10. 0 μg·m L^- 1,the accumulative absorption of Huperize A was increased and its absorption curve was to be linear,with no inhibition due to differentconcentrations. There was no significant difference of absorption parameters of Peff,Kaand faunder conditions of different concentrations（ P 〉0. 05）. The Peff,Kaand faof Huperize A at concentration of 10. 0 μg. m L^- 1in four different regions of rats intestine were in the following sequence： duodenum〉 ileum〉 jejunum 〉colon and the Peff of Huperize Awas（ 0. 57 ± 0. 04） × 10^- 4·cm^- 1·s^- 1,（ 0. 53 ± 0. 02） × 10^- 4·cm^- 1·s^- 1,（ 0. 48 ± 0. 05） × 10^- 4·cm^- 1·s^- 1,（ 0. 41 ± 0. 06） × 10^- 4·cm^- 1·s^- 1. Conclusions： Huperize A could be absorbed at varioussegments of intestinal wall. The absorption of Hup- A appeared as a first- order process with a passive diffusion mechanism.