二氢欧山芹醇乙酸酯在体单灌流肠吸收研究

Study on in Situ Single Pass Perfusion Intestinal Absorption of Columbianetin Acetate

目的研究二氢欧山芹醇乙酸酯在大鼠体内的肠吸收情况。方法运用单向灌流模型、采用高效液相色谱法对药物的质量浓度进行检测来研究药物在不同质量浓度、不同pH值下的吸收。结果二氢欧山芹醇乙酸酯在大鼠4个肠段的Ka,Kapp大小顺序是结肠>回肠>十二指肠>空肠,且结肠、回肠与十二指肠、空肠的Ka,Kapp有显著性差异(P<0.05);在61.93～165.14 mg·L-1内,Ka,Kapp无显著性差异(P>0.05);在pH 3.0至pH 5.0内,Ka,Kapp无显著性差异(P>0.05)。结论二氢欧山芹醇乙酸酯在各肠段均有吸收,其中结肠吸收最好;药物吸收不受质量浓度的影响,在较大质量浓度下(165.14 mg·L-1)也无饱和现象;在肠黏膜的转运为被动扩散过程;药物吸收无pH值依赖性。

OBJECTIVE To study the intestinal absorption behavior of columbianetin acetate. METHODS Single pass perfusion model was used to study the absorption of columbianetin acetate at different drug concentrations and in various pH perfusion solutions respectively. The concentration of columbianetin acetate was determined by HPLC. RESULTS The absorption rate constants （Ka ） and apparent permeability coefficients（ Kapp ） of columbianetin acetate were sequenced as follows colon 〉 ileum 〉 duodenum 〉 jejunum in four different regions of rat intestine. The Ka and Kapp of colon and ileum were significant different from those of duodenum and jejunum （P 〈0. 05）. No difference（ P 〉0. 05） in Ka and Kapp was observed in the concentration ranges of 61.93 - 165.14 mg· L^-1 and in pH ranges of 3 - 5. CONCLUSION Columbianetin acetate can be absorbed in whole intestinal sections and colon is the best absorption region of whole rat intestines. The increase of columbianetin acetate concentration has no effect on absorption kinetics, the absorption of columbianctin acetate is a passive diffusion process. The absorption ot the drug is not pH-dependent.