Development of Ussing model coupled with artificial membrane for predicting intestinal absorption mechanisms of drugs.

Abstract

The absorption mechanisms of drugs play an important role on development and various application of drugs. However, the present methods of absorption mechanisms are not perfect enough. Hence, exploring a novel method to accurately predict the absorption mechanisms is necessary. In this study, we developed an Ussing model coupled with artificial membrane (AM-Ussing) for predicting the permeability of passive diffusion. Furthermore, by the combination of AM-Ussing and Ussing model, the three different mechanisms including efflux transport, uptake transport and passive diffusion could be successfully distinguished. Specifically, 12 drugs of passive transport were selected to evaluate AM-Ussing. And the high permeability correlation between AM-Ussing model and traditional Ussing model indicated that AM-Ussing was successfully established. Moreover, the absorption mechanisms of 11 drugs were predicted by the combination of AM-Ussing and Ussing model. The results showed that three kinds of absorption mechanisms mentioned can be predicted successfully. Therefore, AM-Ussing model is a potential tool to assess passive diffusion, and the combined use of AM-Ussing and Ussing model is an effective method to predict the intestinal absorption mechanisms of drugs.