盐酸麻黄碱的大鼠肠吸收研究

Study on Ephedrine Hydrochloride Intestinal Absorption in Rats

目的:研究盐酸麻黄碱的肠吸收机制。方法:利用大鼠在体单向肠灌流模型,采用HPLC法测定灌流液中盐酸麻黄碱含量,分别考察灌流速度、盐酸麻黄碱质量浓度、不同肠段以及P-糖蛋白抑制剂对盐酸麻黄碱肠吸收的影响。结果:灌流速度对盐酸麻黄碱吸收速率常数(Ka)和表观吸收系数(Papp)有极显著影响(P<0.01);灌流液中盐酸麻黄碱质量浓度对Ka和Papp无显著影响(P>0.05);盐酸麻黄碱在小肠各肠段(十二指肠、空肠和回肠)的Ka和Papp无显著性差异(P>0.05),但其Ka值显著大于在结肠处的值(P<0.05),而各肠段的Papp无显著性差异(P>0.05),P-糖蛋白抑制剂对盐酸麻黄碱在各肠段的Ka和Papp无显著影响(P>0.05)。结论:盐酸麻黄碱在大鼠肠道内的吸收机制为被动扩散,不存在饱和吸收;其在全肠道吸收较好,吸收窗主要在小肠,且小肠内无明显的特定吸收部位;盐酸麻黄碱可能不是P-糖蛋白的底物。

Objective：To study the mechanism of ephedrine hydrochloride intestinal absorption in rats.Methods：The effects of perfusion rate,drug concentration,intestinal segment and P-gp inhibitor on the intestinal absorption of the drug were investigated by using in situ rat single-pass intestinal perfusion （SPIP） model and establishing a HPLC method to determine the drug concentrations in the perfusates.Results：The perfusion rate had a significant effect on the drug absorption rate constant （Ka） and apparent permeability （Papp） （P0.01）,while the drug concentration had no significant effect （P0.05）.The Ka or Papp had no significant difference between different small intestinal segments（duodenum,jejunum and ileum） （P0.05）.The value of Ka in small intestinal segments was significantly larger than that in the colon （P0.05） and the value of Papp had no significance among all the intesinal segments （P0.05）.The Ka or Papp had no significant difference before and after adding P-gp inhibitor in the perfusate （P0.05）.Conclusion：The mechanism of ephedrine hydrochloride intestinal absorption in rats was passive diffusion,and there was no saturated absorption.The drug was well absorbed in all the intestinal segments.The absorption window was mainly attributed to small intestine.Ephedrine hydrochloride may be not a substrate of P-gp as cyclosporin A did not significantly affect the Ka or Papp in different intestinal segments in rats.