| Indication |
For improvement of survival of stable patients with left
ventricular systolic dysfunction (ejection fraction <40%) and
clinical evidence of congestive heart failure after an acute myocardial
infarction. |
| Pharmacodynamics |
Eplerenone, an aldosterone receptor antagonist similar to
spironolactone, has been shown to produce sustained increases in plasma
renin and serum aldosterone, consistent with inhibition of the negative
regulatory feedback of aldosterone on renin secretion. The resulting
increased plasma renin activity and aldosterone circulating levels do
not overcome the effects of eplerenone. Eplerenone selectively binds to
recombinant human mineralocorticoid receptors relative to its binding to
recombinant human glucocorticoid, progesterone and androgen receptors. |
| Mechanism of action |
Eplerenone binds to the mineralocorticoid receptor and thereby
blocks the binding of aldosterone (component of the
renin-angiotensin-aldosterone-system, or RAAS). Aldosterone synthesis,
which occurs primarily in the adrenal gland, is modulated by multiple
factors, including angiotensin II and non-RAAS mediators such as
adrenocorticotropic hormone (ACTH) and potassium. Aldosterone binds to
mineralocorticoid receptors in both epithelial (e.g., kidney) and
nonepithelial (e.g., heart, blood vessels, and brain) tissues and
increases blood pressure through induction of sodium reabsorption and
possibly other mechanisms. |
| Absorption |
The absolute bioavailability of eplerenone is unknown. |
| Volume of distribution |
|
| Protein binding |
50% |
| Metabolism |
Eplerenone is metabolized primarily by CYP3A4, however, no active metabolites have been identified in human plasma. |
| Route of elimination |
Not Available |
| Half life |
4-6 hours |
| Clearance |
- Apparent plasma cl=10 L/hr
|
| Toxicity |
The most likely symptoms of human overdosage would be anticipated
to be hypotension or hyperkalemia. However, no cases of human overdosage
with eplerenone have been reported. |
