药物与细胞膜相互作用的ppKCE动力学参数

摘要

在区段-区段动力学毛细管电泳(ppKCE)的理论基础上,以兔红细胞膜和人红细胞膜为受体,研究了药物跨膜转运的动力学过程,同时测得了表征药物与细胞膜间结合快慢的正向结合速率常数kon、反向解离速率常数koff及配体与受体间相互作用的结合常数Kb.考察了迁移时间及峰高的稳定性、pH值和温度对药物与细胞膜相互作用动力学参数的影响.结果表明,与人体生理pH值一致时,细胞膜具有最大的生物活性,细胞膜与药物的Kb及kon均达到最大值.测定了细胞膜与西酞普兰、依匹斯汀、加替沙星及罗沙替丁相互作用的kon,koff和Kb.采用"时间比法"和紫外-可见吸收光谱法对该方法的准确性进行了验证.本研究为评价药物疗效、研究毒性及药物动力学提供了一种新方法.%Based on the theory of plug-plug kinetic capillary electrophoresis (ppKCE), the rabbit red blood cell membrane and human red blood cell membrane were used to study the kinetic parameters of the interaction between the cell membrane and drug. The rate constants of complex formation kon, the dissociation koff and the binding constant Kb between cell membrane and drugs were directly determined simultaneously. The stability of peak height and migration time was studied. The influence of pH and temperature on the kinetic parameters of the interaction between the cell membrane and drugs were examined and analyzed. The results indicate that at physiological pH value, the cell membrane showed biggest biology activeness, the kon and Kb between cell membrane and drugs reached maximum value. The values of koff, kon and Kb between cell membrane and CIT,Epinastine, Gatifloxacin and Roxatidine were gained. The accuracy of ppKCE was confirmed by the time ratio method and UV-Vis absorption spectra. It could provide a new approach for the evaluation of drug efficiency,toxicity and pharmacokinetics in vivo.