不同分子量美沙拉嗪PEG修饰物的大鼠在体肠吸收研究

摘要

Aim To study the absorption kinetics of se-ries molecular weight 5-ASA-mPEG in rats intestine. Methods The in situ intestinal absorption property of 5-ASA-mPEG in rats was investigated by means of sin-gle-pass perfusion, and HPLC method was established to determine the drug concentration in the perfusate. Results The drug concentration and the site of intes-tine segments had little effect on the drug absorption constant ( Ka ) and apparent absorption coefficient (Papp). The perfusion flow rate and the variable mo-lecular weight of 5-ASA-mPEG could significantly af-fect the Ka and Papp. Conclusion 5-ASA-mPEG can be absorbed at all segments of the intestine of rats and has no specific absorption site. It is preliminarily in-ferred that the absorption mechanism of 5-ASA-mPEG is passive transportation. The intestinal absorption of 5-ASA-mPEG shows a downward trend with the increase in molecular weight. The results shows that the modifi-cation of 5-ASA by PEG can effectively inhibit the in-testinal absorption of mesalazine.%目的：对系列分子量的美沙拉嗪PEG修饰物(5-ASA-mPEG)的大鼠肠道吸收动力学特征进行考察。方法采用单向灌流技术考察5-ASA-mPEG的大鼠在体肠吸收性质，以高效液相色谱法测定灌流液中药物的浓度。结果考察范围内药物浓度及药物吸收部位对药物吸收速率常数( Ka )和表观吸收系数( Papp )无显著性影响。灌流速度及5-ASA-mPEG分子量在考察范围内对Ka 及Papp具有明显影响。结论5-ASA-mPEG修饰物在全肠道均有吸收，无明显吸收特定部位，初步判定其吸收机制为被动扩散；随5-ASA-mPEG分子量提高，其肠道吸收呈下降趋势，表明PEG修饰能够抑制5-ASA的肠道吸收过程。