Yamashita S, Masada M, Nadai T, Kimura T
Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
J Pharm Sci. 1990 Jul;79(7):579-83. doi: 10.1002/jps.2600790706.
Effects of disodium ethylenediaminetetraacetate (EDTA) and bile salts on the ion-selective permeability and electrical resistance (Rm) of rat jejunal membrane were investigated in vitro to characterize the enhanced permeability to drugs by these adjuvants. Ion-selective permeability was estimated from diffusion potentials across the membrane and expressed as permeability ratios for ions (Pcl/PNa, PK/PNa). Pretreatment of the mucosal membrane with EDTA increased PCl/PNa and decreased Rm. At the same time, the mucosal-to-serosal flux rate of sulfanilic acid (SA), a model of polar drugs, was enhanced. The relationship between Pcl/PNa and SA flux rate after pretreatment with EDTA was demonstrated to yield a curve asymptotic to the free mobility ratio of those ions. When bile salts were used as the pretreatment agent, instead of EDTA, similar results to the case of EDTA were obtained. Assuming that EDTA interacts with the tight junctional portion of the mucosal membrane to enhance the paracellular permeability to drugs selectively, as demonstrated in many other reports, changes in PCl/PNa and Rm were assumed to correspond to structural change in the tight junction. Consequently, we suggest that these factors can be useful parameters when considering the mechanism of enhanced permeability of the intestinal membrane by several adjuvants.
