Antagonism of aldosterone in normal subjects by Ro 12-2503 and spironolactone

The potency and efficacy of a single dose of a new aldosterone antagonist, potassium 17a-hydroxy-6β,7β-methylene-3-oxo-D-homo-17aα-pregna-4,16-diene-21-carbox ylate (Ro 12-2503), in reversing the renal effects of exogenous aldosterone were compared to those of spironolactone, and placebo. The study was performed according to double-blind and crossover procedure in six healthy male subjects. Both drugs, spironolactone and Ro 12-2503, did not completely antagonize the effects of aldosterone. The efficacy of Ro 12-2503 in terms of the urinary Na⁺/K⁺ ratio and the urinary Na⁺ concentration was less than that of spironolactone. Spironolactone produced a slightly greater natriuresis, but the difference was not significant. The method described, based on standard bioassay techniques permits a comparison of the two drugs, and may prove useful in the screening and evaluation of aldosterone antagonists.