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Comparison of prorenoate potassium and spironolactone after repeated doses and steady state plasma levels of active metabolites.
Author(s) -
McInnes GT,
Shelton JR,
Harrison IR,
Perkins RM,
Palmer RF
Publication year - 1982
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1982.tb01354.x
Subject(s) - fludrocortisone , aldosterone , spironolactone , chemistry , potassium , endocrinology , mineralocorticoid , steady state (chemistry) , medicine , hyperkalemia , pharmacokinetics , sodium , pharmacology , excretion , hydrocortisone , biochemistry , organic chemistry
1 After repeated single daily doses, the aldosterone antagonists prorenoate potassium and spironolactone were compared with regard to renal antimineralocorticoid activity, plasma potassium concentration and steady state plasma levels of their active metabolites, prorenone and canrenone respectively, in a balanced crossover study of twelve healthy subjects. 2 Following challenge with the mineralocorticoid, fludrocortisone, best estimates of the potency of prorenoate potassium relative to spironolactone were 3.6 (95% confidence limits 1.6‐10.4) for urinary sodium excretion and 3.4 (95% confidence limits 2.0‐6.5) for urinary log10 10Na/K. Estimates with respect to urinary potassium excretion and plasma potassium concentration were imprecise, confirming the limitations of the fludrocortisone model in the evaluation of aldosterone antagonists at steady state. 3 Both compounds exhibited directly proportional relationships between daily dose and steady state plasma levels of active metabolites. The approximate mean terminal elimination half‐life of prorenone at steady state was 32.6 h (range 18‐ 80 h).