Plasma levels of canrenone and androgen receptoractive materials (ARM) were determined during long-term oral K-canrenoate or spironolactone therapy in cirrhotics with chronic recurrent ascites. Mean plasma canrenone level was approximately 3 times higher under K-canrenoate than under spironolactone treatment; moreover, the levels were not dose related. Either type of treatment did not affect plasma aldosterone and testosterone concentrations. Plasma ARM during K-canrenoate treatment did not change, whereas in the spironolactone group a 3-fold increase of ARM occurred (p <0.05). No dose-related effect was evident with the latter treatment. The lower incidence of gynecomastia in the K-canrenoate group was not correlated with values of plasma canrenone or ARM (p > 0.05).
Our study questions the traditional view that the mode of action of spironolactone is via its metabolite canrenone. The two antialdosterone drugs, although equally effective in clearing ascites from cirrhotics, appear to act through partially different metabolites. The lower incidence of antiandrogenic or estrogen-like side effects during K-canrenoate seems to be related to metabolites other than canrenone itself.