Conversion of spironolactone to 7 alpha-thiomethylspironolactone by hepatic and renal microsomes.

Recent observations indicate that 7 alpha-thiomethylspironolactone is an important circulating metabolite of the mineralocorticoid antagonist spironolactone (SL). Studies were carried out to determine possible sites and pathways of 7 alpha-thiomethyl-SL formation and, in particular, to evaluate SL metabolism by guinea pig hepatic and renal microsomal preparations. In the absence of S-adenosylmethionine (SAM), liver and kidney microsomes rapidly converted SL to 7 alpha-thio-SL as the only metabolite.