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The nonsurfactant adjuvants diethyl maleate (DEM) and diethyl ethoxymethylenemalonate (DEEMM) were previously shown to enhance the colonic absorption of the hydrophilic drug cefmetazole in rats and to concomitantly decrease the non-protein sulfhydryl concentration of colonic tissue. To test further an association between nonprotein sulfhydryl concentration and membrane permeability, the effects of several adjuvants, DEM, DEEMM, ethanol and sodium salicylate, were tested in the everted sac preparation of rat colon and jejunum. There was a good correlation between decreased nonprotein sulfhydryl concentration and enhanced cefmetazole absorption in both tissues. Moreover, the addition of cysteamine reversed the effects of each adjuvant on nonprotein sulfhydryls and cefmetazole absorption. These results suggest that tissue levels of nonprotein sulfhydryls regulate at least in part the intestinal membrane permeability. |
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