药物从人小肠上皮细胞模型排放的动力学模型

THE STUDY OF KINETIC MODEL FOR THE DRUG EFFLUX FROM A HUMAN INTESTINAL EPITHELIAL MEMBRANE MODEL SYSTEM

一种体外培养的人小肠上皮细胞模型（Ｃａｃｏ－２）已应用于药物在小肠细胞中的摄入、排放和过细胞输运等过程的研究。本工作旨在对排放过程的动力学模型进行探讨。实验测定多种药物在Ｃａｃｏ－２细胞模型的排放，分别用动力学一级、二级及多项式方程对排放进行数据拟合，用ＡＩＣ（Ａｋａｉｋｅ’ｓｉｎｆｏｒｍａｔｉｏｎｃｒｉｔｅｒｉｏｎ）值评判拟合的优劣，并将拟合结果与实际排放作比较。结果：动力学二级模型的拟合度最好，由拟合得到的排放初速和最大排放量等数据与实验量相符合。结论：药物从Ｃａｃｏ－２细胞的排放是表观二级的。由此可以计算药物排放的初速、最大排放量及半衰期等重要的动力学参数。

PURPOSE A human intestinal epithelial membrane model system(Caco-2) cultured in vitro had been applied to study the drug uptake, efflux and transepithelial transport at small intestine. In this work the kinetic models of the efflux were studied.METHODS The efflux of several drugs was determined using the Caco-2model. all experimental data were fitted with first-order, second-order of kinetic equations and multinomial equation in order to find the best one according to the AIC(Akaike's information criterion).Then take the fitted data to compare with the experimental data. RESULTS The second-order model was the best one. The initial rate and the maximum efflux amount from fitted equation were best closely with the experiment data.CONCLUSIONS The drug efflux is apparent second-order course. So some important kinetic parameters such as initial rate,maximum efflux amount and half-life time of the drug efflux can be calculated.