Chemical Property of CID 9953590
Chemical Property:
- Appearance/Colour:White solid
- Vapor Pressure:0mmHg at 25°C
- Melting Point:241-243 °C
- Refractive Index:1.587
- Boiling Point:597.933 °C at 760 mmHg
- Flash Point:259.474 °C
- PSA：82.20000
- Density:1.31 g/cm3
- LogP:3.12450
- Storage Temp.:Store at RT
- Solubility.:DMSO: soluble2mg/mL, clear (warmed)
- XLogP3:1.4
- Hydrogen Bond Donor Count:0
- Hydrogen Bond Acceptor Count:6
- Rotatable Bond Count:2
- Exact Mass:414.20423867
- Heavy Atom Count:30
- Complexity:907
- Purity/Quality:
-
99% HPLC *data from raw suppliers
Eplerenone *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
-
SDS file from LookChem
Useful:
- Canonical SMILES:CC12CCC(=O)C=C1CC(C3C24C(O4)CC5(C3CCC56CCC(=O)O6)C)C(=O)OC
- Isomeric SMILES:C[C@]12CCC(=O)C=C1C[C@H]([C@@H]3[C@]24[C@H](O4)C[C@]5([C@H]3CC[C@]56CCC(=O)O6)C)C(=O)OC
- Recent EU Clinical Trials:Patiromer-facilitated, dose-escalation of mineralocorticoid antagonists for the management of worsening congestion in people with heart failure and hyperkalaemia.
-
Description
Eplerenone is used alone or in combination with other medications to treat high blood pressure. Eplerenone is in a class of medications called mineralocorticoid receptor antagonists. It works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure. Eplerenone is a mineralocorticoid receptor antagonist. It is selective for the mineralocorticoid receptor over glucocorticoid, androgen, progesterone, and estrogen receptors in radioligand binding assays (IC50s = 138, 6,920, 523, >10,000, and 5,702 nM, respectively). Eplerenone inhibits aldosterone-induced mineralocorticoid activity in a luciferase assay (IC50 = 122 nM). In vivo, eplerenone (100 mg/kg per day) reduces urinary albumin secretion and glomerulosclerosis in the Dahl salt-sensitive rat model of hypertension and nephropathy. It reduces myocardial IL-1β levels and collagen deposition, as well as improves left ventricular systolic dysfunction in a mouse model of acute myocardial infarction. Formulations containing eplerenone have been used in the treatment of hypertension and heart failure after myocardial infarction. Eplerenone derives its antihypertensive effect by blocking the binding of aldosterone
at the mineralocorticoid receptor (MR). The drug, which was previously approved
only for the oral treatment of hypertension, is now indicated to improve survival of
stable patients with left ventricular systolic dysfunction (ejection fraction ＜40%) and
clinical evidence congestive heart failure (CHF) after an acute myocardial infarction.
Aldosterone is a key hormone in the renin-angiotensin-aldosterone system (RAAS),
which is of critical importance in the development and progression of hypertension,
cardiac remodeling and other cardiovascular diseases. The purpose of RAAS is to
control sodium, potassium, and fluid volume balance. Aldosterone binds to MRs 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. The actions of aldosterone can be blocked by
spironolactone (Aldactone ?), a relatively nonselective MR antagonist that has been
used in clinical practice for many years. Eplerenone, a structural analog of
spironolactone, is a highly selective MR antagonist, with significantly lower affinity
for other nuclear receptors. It can be prepared by several related ways, with the key
step being the introduction of 11-a-hydroxy group on the steroid scaffold via
microbiological conversion. The presence of the 11-a-hydroxy group permits the
derivation of the epoxy functionality found in eplerenone. Following oral
administration, eplerenone is well absorbed and reaches peak plasma concentrations
in～2 h. The bioavailability of eplerenone is 98% and it is cleared predominantly by
CYP3A4 metabolism, with an elimination half-life of 4–6 h. Steady state is reached
within two days. Eplerenone therapy is typically initiated with 25 mg once daily oral
dosing and, if tolerated by the patient, titrated to 50 mg once daily. In a clinical
study, eplerenone significantly reduced deaths in congestive heart failure patients
after a heart attack, above and beyond standard therapy, including ACE inhibitors
and β-blockers. The trial in more than 6600 hospitalized patients demonstrated a
15% reduction in the risk of death for eplerenone compared with placebo, in addition
to standard treatment. The most commonly reported adverse events associated with
eplerenone are hyperkalemia and increased creatine.
-
Uses
Selective aldosterone receptor antagonist (SARA), structurally similar to Spiranolactone. Eplerenone is used alone or in combination with other medications to treat high blood pressure. Eplerenone is in a class of medications called mineralocorticoid receptor antagonists. It works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure. Eplerenone is an aldosterone antagonist with an IC50 of 0.36 μM. It is used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone, though it may be more specific for the mineralocorticoid receptor and is sp anticancer agent
-
Clinical Use
A newer drug, eplerenone, has a structure similar to that of spironolactone and a similar mechanism of action. It was initially approved for use in the treatment of
hypertension but it can now be used in the treatment of patients with left ventricular systolic dysfunction and congestive heart failure after myocardial infarction.
-
Drug interactions
Potentially hazardous interactions with other drugsACE inhibitors or AT-II antagonists: enhanced
hypotensive effect; risk of severe hyperkalaemia.Anti-arrhythmics: concentration increased by
amiodarone - reduce eplerenone dose.amiodarone - reduce eplerenone dose.
Antibacterials: concentration increased by
clarithromycin and telithromycin - avoid;
concentration increased by erythromycin - reduce
eplerenone dose; concentration reduced by rifampicin
- avoid; avoid with lymecycline; increased risk of
hyperkalaemia with trimethoprim.Antidepressants: concentration reduced by St John’s
wort - avoid; increased risk of postural hypotension
with tricyclics; enhanced hypotensive effect with
MAOIs.Antiepileptics: concentration reduced by
carbamazepine, fosphenytoin, phenytoin,
phenobarbital and primidone - avoid.Antifungals: concentration increased by itraconazole
and ketoconazole - avoid; concentration increased by
fluconazole - reduce eplerenone dose.Antihypertensives: enhanced hypotensive effect,
increased risk of first dose hypotensive effect with
post-synaptic alpha-blockers.Antivirals: concentration increased by ritonavir -
avoid; concentration increased by saquinavir - reduce
eplerenone doseCiclosporin: increased risk of hyperkalaemia and
nephrotoxicityCytotoxics: increased risk of nephrotoxicity and
ototoxicity with platinum compounds.NSAIDs: increased risk of hyperkalaemia (especially
with indometacin); increased risk of nephrotoxicity;
antagonism of diuretic effect.Potassium salts: increased risk of hyperkalaemia.Lithium: reduced lithium excretion - avoidTacrolimus: increased risk of hyperkalaemia and
nephrotoxicity.CYP3A4 inhibitors: Do not exceed a dose of 25 mg
daily for eplerenone.CYP3A4 inducers: reduced eplerenone
concentration - avoid.
