Activity of sulfur-containing intermediate metabolites of spironolactone

• Published in: Clinical pharmacology and therapeutics Vol. 27; no. 3; p. 363
• Main Authors: McInnes, G T, Asbury, M J, Shelton, J R, Harrison, I R, Ramsay, L E, Venning, G R, Clarke, J M
• Format: Journal Article
• Language: English
• Published: United States 01.03.1980
• Subjects: Adult; Aldosterone; Diuresis - drug effects; Humans; Mineralocorticoid Receptor Antagonists; Spironolactone - metabolism; Spironolactone - pharmacology; Structure-Activity Relationship
• ISSN: 0009-9236
• DOI: 10.1038/clpt.1980.48

The renal antimineralocorticoid activity of single administration of 2 sulfur-containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes indiced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 alpha-thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 alpha-thio-spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 alpha-thiomethyl-spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur-containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone.