Influence of various anions on intestinal disappearance of hexamethonium chloride and pralidoxime chloride in rats.

The intestinal transfer of two poorly absorbed quaternary ammonium drugs, hexamethonium chloride (I) and pralidoxime chloride (II), in the presence of various organic and inorganic anions was investigated in the rat using a modified in situ gut technique. The results were in agreement with those of the conventional in situ loop and plasms drug level techniques. Of the anions investigated, cholate, desoxycholate, taurocholate, phoscholate, dehydrocholate, and hyodesoxycholate had the greatest effect on increasing the amount and rate of disappearance of I. Similarly, the amount and rate of disappearance of II were enhanced markedly in the presence of phoscholate and trichloroacetate. The effect of cholate and phoscholate was investigated in detail. The membrane permeability and histological studies indicated that these anions may compromise the structural integrity of the membrane tissue, thus enhancing drug transfer.