Multiple dose kinetics of spironolactone and canrenoate-potassium in cardiac and hepatic failure |
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Authors: | W. Sadée R. Schröder E. v. Leitner M. Dagcioglu |
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Affiliation: | (1) Kardiologische Abteilung, Klinikum Steglitz, Freie Universität Berlin, Germany;(2) Clinical Pharmacology and Pharmacokinetics Sections, Schools of Medicine and Pharmacy, University of Southern California, Los Angeles, California, USA |
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Abstract: | Summary Plasma concentrations of canrenone and canrenoate were measured in 43 patients treated with spironolactone 50–400 mg/day, and in one patient treated with canrenoate-K 3×200 mg/day. The cumulation of canrenone and canrenoate was followed in 9 patients recovering from myocardial infarction, without congestive heart failure or cirrhosis, who received spironolactone 2×100 mg/day. The cumulation half-life was 1–4 days, which may partly explain the delayed clinical action of spironolactone. The plasma elimination half-life of canrenone and canrenoate in six of these patients lay between 13.5 and 24 h. After 10 doses it was unchanged in three patients and had decreased only slightly in three others. Steady state minimum plasma levels of canrenone and canrenoate were measured in 33 patients with congestive heart failure or cirrhosis who received spironolactone 50–400 mg/day for at least three weeks. There was up to 15 fold inter-individual variation in the plasma levels of canrenone amongst those receiving spironolactone 200 mg/day. No statistically significant correlation was found between steady state levels of canrenone and plasma creatinine or the results of bromsulphalein liver function tests. In one patient with severe congestive heart failure given canrenoate-K 3×200 mg/day, cumulation of canrenone and canrenoate occurred for seven days, followed by a gradual decline in their plasma levels until the eleventh day of therapy. A loading dose is recommended for initiation of spironolactone therapy. |
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Keywords: | Spironolactone canrenone canrenoate cardiac failure cirrhosis aldosterone antagonist |
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