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Effect of chronic heart failure on the pharmacokinetics of eplerenone following single and multiple dosing
Author(s) -
Ravis W. R.,
Reid S.,
Van Ess P. J.,
Ferry J.,
Tolbert D.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.141
Subject(s) - eplerenone , medicine , pharmacokinetics , heart failure , cmax , clinical pharmacology , dosing , aldosterone , pharmacology , cardiology , myocardial infarction , spironolactone
This study determined the effect of chronic congestive heart failure (CHF) on the single‐ and multiple‐dose pharmacokinetics of eplerenone (EPL). EPL is a highly selective aldosterone blocker indicated for the treatment of hypertension with demonstrated morbidity/mortality benefits in acute myocardial infarction patients with left ventricular heart failure. Eight subjects with CHF and 8 matched‐control subjects (matched for age, sex, and weight) were enrolled in a 2‐period, open‐label, single‐ and multiple‐dose study. After a single 50‐mg dose and multiple once daily 50‐mg doses, pharmacokinetic parameters were determined for EPL, its inactive ring‐open form, SC‐70303, and the inactive metabolite, SC‐71597. No statistically significant differences in any EPL, SC‐70303, or SC‐71597 pharmacokinetic parameters were observed between CHF and control subjects. Following multiple‐dosing, EPL CL/F was insignificantly lower (<27.4%) in CHF subjects compared with control subjects resulting in an insignificant increase in EPL AUC (<37.7%) and C max (<29.7%). As expected from the pharmacology of EPL, mean serum aldosterone and active renin values increased in both subject groups following administration of EPL. CHF subjects had a reduction in mean Na + retention scores from 1.88 pre‐ to 0.5 post‐treatment. EPL was well tolerated in both subject groups. These results indicate that dose adjustment based on pharmacokinetic alterations does not appear necessary in CHF patients. Clinical Pharmacology & Therapeutics (2004) 75 , P37–P37; doi: 10.1016/j.clpt.2003.11.141