Potassium-sparing renal effects of trimethoprim and structural analogues

Background/Aims: The antibiotic antagonists of folic acid trimethoprim, tet roxoprim, pyrimethamine and their antineoplastic analogue methotrexate have structural characteristics in common with the potassium-sparing diuretic t riamterene. They may, therefore, share with triamterne potassium-sparing re nal effects. Methods: Clearance studies were performed on anesthetized male Sprague-Dawley rats, and the drug effects on glomerular filtration rate an d on urinary excretion of sodium, chloride, and potassium were studied. Res ults: Trimethoprim and tetroxoprim, injected intravenously at doses ranging from 0.3 to 30 mg/kg, induced dose-dependent natriuretic and antikaliureti c renal effects, whereas pyrimethamine at doses ranging from 1 to 10 mg/kg and methotrexate at doses ranging from in to 50 mg/kg did not affect urinar y sodium and potassium excretion. An antikaliuretic effect was also observe d after application of the structurally related antiprotozoal compound pent amidine at doses ranging from 3 to 10 mg/kg. In contrast to trimethoprim an d tetroxoprim, the antikaliuresis was accompanied by a marked decrease of u rinary sodium and chloride excretion at all of the doses tested. At 10 mg/k g, pentamidine induced a pronounced fall of the glomerular filtration rate (by 43.5%). Conclusions: Trimethoprim and tetroxoprim share with potassium- sparing diuretics natriuretic and antikaliuretic renal effects which may be caused by similar mechanisms in the distal nephron, whereas pyrimthamine a nd methotrexate do not. A depression of renal hemodynamics is an important factor involved in the antikaliuretic effect of pentamidine. Copyright (C) 2000 S. Karger AG. Basel.