Metabolism of spirolactones by the rat testis in vitro

Spironolactone (SPIR) has been shown in numerous clinical studies to produce sexual disorders. We studied the metabolism of canrenone (CAN), the main metabolite of SPIR, and of the analogue 6,7-dihydrocanrenone (DHC) by the rat testis in vitro. The metabolites produced during a 4 h incubation period were isolated by HPLC and identified by nmr-, ms-, ir- and uv-spectrometry. SPIR was not metabolised in a detectable amount. CAN was converted to canrenoic acid, several hydroxylated (15 beta-, 16 alpha-, 19-, 2OR- and 21S-OH-CAN) and one reduced metabolite (3 alpha-OH-CAN). When DHC was incubated, an analogous pattern was detected. It is concluded that CAN and DHC serve as substrates for steroid metabolism in the rat testis.