Assessment of the antimineralocorticoid effect of RU 28318 in healthy men with induced exogenous and endogenous hypermineralocorticism.
The antimineralocorticoid effect of a single dose of RU 28318, has been assessed in healthy men with exogenous or endogenous hypermineralocorticism. For exogenous hypermineralocorticism induced by ingestion of 9 alpha-fluorohydrocortisone (9 alpha-FHC) and aldosterone infusion, RU 28318 100 mg (9 alpha-FHC ingestion) or 200 mg (aldosterone infusion) was administered, and its effect compared with identical doses of spironolactone or a placebo. For endogenous hypermineralocorticism induced by ingestion of furosemide, RU 28318 100 and 300 mg was tested in comparison with 100 mg spironolactone or placebo. In all 3 studies, both RU 28318 and spironolactone significantly raised the urinary Na/K ratio when compared to placebo administration. No significant difference was apparent between RU 28318 and spironolactone. Thus, a single dose of RU 28318 in man has an antimineralocorticoid effect identical to those produced by the identical molar dose of spironolactone. In addition, the results show that furosemide-induced hyperaldosteronism constitutes a simple and reproducible test for assessing the antimineralocorticoid effect of a drug.
D000328:Adult; D000450:Aldosterone / Q000009:adverse effects; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D005438:Fludrocortisone / Q000009:adverse effects; D005665:Furosemide / Q000009:adverse effects; D006801:Humans; D006929:Hyperaldosteronism / Q000139:chemically induced*; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; C041006:RU 28318; D005665:Furosemide; D012964:Sodium; D011188:Potassium; D005438:Fludrocortisone