the effect of trimethoprim on sodium transport across the frog skin epithelium trimethoprim a dihydrofolate reductase inhibitor is used as a therapeutical agent in combination with sulfamethoxazole studies of the interaction of trimethoprim with membrane transport are rare this paper presents a study of the effect of trimethoprim on the shortcircuit current isc and on the transepithelial total conductance gt of the isolated frog skin we found a fast drop less than 1 min of isc 50 and gt 30 after the addition of the drug to the outside medium mucosa a doseresponse curve of the effect of the drug has shown that trimethoprim has no effect for concentrations below 001 mm and reaches a halfmaximum inhibition at 05 mm trimethoprim induces a decrease in the sodium radioactive tracer fluxes that parallel the decrease of the observed isc it induces a hyperpolarization of the mucosal barrier in the same way that amiloride does a comparative study of the effect of trimethoprim and amiloride has shown that trimethoprim acts on the amiloridesensitive sodium channels of the mucosal barrier and behaves as a competitive inhibitor of amiloride with a dissociation constant ktrim of 53 x 105 m while kamil 46 x 108 m