Multiple dose kinetics of spironolactone and canrenoate-potassium in cardiac and hepatic failure

Comparison of prorenoate potassium and spironolactone after repeated doses and steady state plasma levels of active metabolites.

“…At steady state the plasma potassium results revealed evidence of treatment effects but differences were slight and did not allow valid estimation of relative potency. However, these influences were more marked on day 11 suggesting significant positive log aldosterone antagonist dose-plasma potassium response relationships in conditions of mineralocorticoid excess, and allowing a valid estimate of relative potency, prorenoate potassium: spironolactone, (Karim et al, 1976c;Ramsay & Hettiarachchi, 1981;Sadee et al, 1974). This study provides a comprehensive description of the steady state plasma levels of the active metabolite of each aldosterone antagonist, extending previous less complete information (Karim et al, 1976c;McInnes et al, 1981;Ramsay etal., 1977a;Ramsay & Hettiarachchi, 1981;Sadee et al, 1974).…”

“…However, these influences were more marked on day 11 suggesting significant positive log aldosterone antagonist dose-plasma potassium response relationships in conditions of mineralocorticoid excess, and allowing a valid estimate of relative potency, prorenoate potassium: spironolactone, (Karim et al, 1976c;Ramsay & Hettiarachchi, 1981;Sadee et al, 1974). This study provides a comprehensive description of the steady state plasma levels of the active metabolite of each aldosterone antagonist, extending previous less complete information (Karim et al, 1976c;McInnes et al, 1981;Ramsay etal., 1977a;Ramsay & Hettiarachchi, 1981;Sadee et al, 1974). Peak plasma levels occurred 2-3 h after the daily dose of each drug confirming evidence from single dose studies (Karim et al, 1976b;unpublished observations) and the ratio of minimum to maximum steady state plasma levels was about 20% in each case, indicating that both drugs displayed rapid gastrointestinal absorption and that appreciable blood levels were present 24 h after treatment.…”

Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses.

“…Steady state levels of spironolactone metabolites in plasma are achieved only after several days administration (Sadee, Schroder, Leitner & Dagcioglu, 1974), and in the clinical situation there is a similar delay in observing the peak pharmacological effect of spironolactone. The latter observation led to the suggestion that single dose bioassay methods are inappropriate for testing aldosterone antagonists (Lant et aL., 1966).…”

The pharmacodynamics of single doses of prorenoate potasssium and spironolactone in fludrocortisone treated normal subjects.

“…In clinical practice spironolactone is frequently prescribed in four daily doses. The profile of pharmacological activity observed in this study, particularly when considered in conjunction with the multiple dose pharmacokinetics of spironolactone (Sadee, Schroder, Leitner & Dagcioglu, 1974), suggests that such frequent administration may be unnecessary, and that twelve hourly or once daily dosage with spironolactone may be equally satisfactory. The latter regimes would have the advantage of greater convenience for the patient.…”