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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H30O6
Molecular Weight 414.4914
Optical Activity UNSPECIFIED
Defined Stereocenters 8 / 8
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EPLERENONE

SMILES

[H][C@@]12C[C@@]3(C)[C@@]([H])(CC[C@@]34CCC(=O)O4)[C@]5([H])[C@@H](CC6=CC(=O)CC[C@]6(C)[C@@]15O2)C(=O)OC

InChI

InChIKey=JUKPWJGBANNWMW-VWBFHTRKSA-N
InChI=1S/C24H30O6/c1-21-7-4-14(25)10-13(21)11-15(20(27)28-3)19-16-5-8-23(9-6-18(26)30-23)22(16,2)12-17-24(19,21)29-17/h10,15-17,19H,4-9,11-12H2,1-3H3/t15-,16+,17-,19+,21+,22+,23-,24-/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/cdi/eplerenone.html

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. 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. Used 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.

Originator

Curator's Comment: # Novartis

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
122.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
INSPRA

Approved Use

INSPRA is an aldosterone antagonist indicated for: Improving survival of stable patients with LV systolic dysfunction (LVEF ≤40%) and CHF after an acute myocardial infarction. Hypertension, alone or combined with other agents.

Launch Date

1.03299842E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.49 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EPLERENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
18.4 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EPLERENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.01 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EPLERENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
38.2%
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
EPLERENONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Other AEs: Arthralgia, Dizziness...
Other AEs:
Arthralgia (6%)
Dizziness (6%)
Leg cramps (6%)
Infection respiratory (13%)
Sinusitis (2%)
Nausea (4%)
Sources:
400 mg 1 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 21-80 years
n = 56
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 56
Sources:
Other AEs: Dizziness, Nausea...
Other AEs:
Dizziness (2%)
Nausea (5%)
Sources:
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Other AEs: Palpitations, Diarrhoea...
Other AEs:
Palpitations (below serious, 1 patient)
Diarrhoea (below serious, 1 patient)
Fatigue (below serious, 2 patients)
Vessel puncture site reaction (below serious, 1 patient)
Fungal skin infection (below serious, 1 patient)
Nasopharyngitis (below serious, 3 patients)
Dizziness (below serious, 2 patients)
Headache (below serious, 5 patients)
Pollakiuria (below serious, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Infection respiratory 13%
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Sinusitis 2%
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Nausea 4%
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Arthralgia 6%
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Dizziness 6%
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Leg cramps 6%
200 mg 2 times / day multiple, oral
Highest studied dose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy, 21-80 years
n = 48
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 48
Sources:
Dizziness 2%
400 mg 1 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 21-80 years
n = 56
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 56
Sources:
Nausea 5%
400 mg 1 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: multiple
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 21-80 years
n = 56
Health Status: unhealthy
Condition: hypertension
Age Group: 21-80 years
Sex: M+F
Population Size: 56
Sources:
Diarrhoea below serious, 1 patient
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Fungal skin infection below serious, 1 patient
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Palpitations below serious, 1 patient
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Pollakiuria below serious, 1 patient
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Vessel puncture site reaction below serious, 1 patient
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Dizziness below serious, 2 patients
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Fatigue below serious, 2 patients
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Nasopharyngitis below serious, 3 patients
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Headache below serious, 5 patients
50 mg 1 times / day multiple, oral
Dose: 50 mg, 1 times / day
Route: oral
Route: multiple
Dose: 50 mg, 1 times / day
Sources:
healthy
n = 15
Health Status: healthy
Population Size: 15
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: coadministered with ketoconazole increased elperenone AUC by 5.5-fold and Cmax by 1.7-fold and with erythromycin increased AUC by 1.8-fold and Cmax 61%
Page: 9, 10, 15
no
yes
yes (co-administration study)
Comment: coadminstration with fluconazole increased eplerenone AUC by 2.2-fold and Cmax by 1.4-fold
Page: 10.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Recent studies with eplerenone, a novel selective aldosterone receptor antagonist.
2001 Apr
Eplerenone (GD Searle & Co).
2001 Apr
Aldosterone as a mediator of progressive renal disease: pathogenetic and clinical implications.
2001 Apr
Exciting new drugs on the horizon - eplerenone, a selective aldosterone receptor antagonist (SARA).
2001 Aug
The EPHESUS trial: eplerenone in patients with heart failure due to systolic dysfunction complicating acute myocardial infarction. Eplerenone Post-AMI Heart Failure Efficacy and Survival Study.
2001 Jan
New treasures from old? EPHESUS. Eplerenome Post-AHI Heart Failure Efficacy and Survival Study.
2001 Jan
Aldosterone 2001.
2001 Oct
Expanding the outcomes in clinical trials of heart failure: the quality of life and economic components of EPHESUS (EPlerenone's neuroHormonal Efficacy and SUrvival Study).
2002 Apr
Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension.
2002 Aug
Efficacy of eplerenone added to renin-angiotensin blockade in hypertensive patients.
2002 Aug
Do diuretics and aldosterone receptor antagonists improve ventricular remodeling?
2002 Dec
Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5.
2002 Dec
Effects of long-term monotherapy with eplerenone, a novel aldosterone blocker, on progression of left ventricular dysfunction and remodeling in dogs with heart failure.
2002 Dec 3
Results from late-breaking clinical trial sessions at the American College of Cardiology 51st Annual Scientific Session.
2002 Jul 3
Interconversion pharmacokinetics of eplerenone, a selective aldosterone blocker, and its lactone-ring open form.
2002 Jun
Aldosterone as a mediator in cardiovascular injury.
2002 Mar-Apr
New biology of aldosterone, and experimental studies on the selective aldosterone blocker eplerenone.
2002 Nov
The role of aldosterone receptor blockade in the management of cardiovascular disease.
2002 Oct
Gateways to Clinical Trials.
2002 Sep
New antihypertensive drug class.
2003 Apr
Hypertension, angiotensin II, aldosterone, and race.
2003 Apr 2
Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.
2003 Apr 3
Aldosterone blockade and heart failure.
2003 Apr 3
Primary aldosteronism - treatment options.
2003 Aug
Eplerenone: a selective aldosterone blocker.
2003 Fall
Transgenic model of aldosterone-driven cardiac hypertrophy and heart failure.
2003 Jul 11
Eplerenone in patients with left ventricular dysfunction.
2003 Jul 3
[Anti-angiogenic effects of aldosterone antagonists in the fibrin chamber in rats].
2003 Jul-Aug
Hyperkalemia, congestive heart failure, and aldosterone receptor antagonism.
2003 Jul-Aug
Gateways to clinical trials.
2003 Jun
Effect of eplerenone, a selective aldosterone blocker, on blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apolipoprotein E-deficient mice.
2003 Jun
Eplerenone.
2003 Mar
Aldo is back: recent advances and unresolved controversies in hyperaldosteronism.
2003 Mar
Early inflammatory responses in experimental cardiac hypertrophy and fibrosis: effects of 11 beta-hydroxysteroid dehydrogenase inactivation.
2003 Mar
Aldosterone receptor blockade: a therapy resurrected.
2003 Mar-Apr
Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats.
2003 May
Pharmacokinetics and metabolism of [14C]eplerenone after oral administration to humans.
2003 Nov
Long-term safety and efficacy of the selective aldosterone blocker eplerenone in patients with essential hypertension.
2003 Sep
Patents

Sample Use Guides

In Vivo Use Guide
Congestive heart failure post-myocardial infarction: Initial dosage: 25 mg orally once daily. Dosage should titrated to the target dose of 50 mg once daily preferably within 4 weeks. Usual Adult Dose for Hypertension 50 mg orally once daily. Patients with an inadequate blood pressure response should be increased to 50 mg twice a day.
Route of Administration: Oral
Eplerenone (10uM) significantly decreased corticosterone- (0.81 fold compared to treatment with corticosterone alone) and 11-DHC-driven (0.64 fold compared to treatment with 11-DHC alone) mouse VSMC calcification
Name Type Language
EPLERENONE
HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
EPLERENONE [JAN]
Common Name English
EPLERENONE [ORANGE BOOK]
Common Name English
INSPRA
Brand Name English
EPLERENONE [MI]
Common Name English
eplerenone [INN]
Common Name English
EPLERENONE [EP MONOGRAPH]
Common Name English
EPLERENONE [VANDF]
Common Name English
SC-66110
Code English
PREGN-4-ENE-7,21-DICARBOXYLIC ACID, 9,11-EPOXY-17-HYDROXY-3-OXO-, G-LACTONE, METHYL ESTER, (7.ALPHA.,11.ALPHA.,17.ALPHA)-
Common Name English
9,11?-Epoxy-17-hydroxy-3-oxo-17?-pregn-4-ene-7?,21-dicarboxylic acid, ?-lactone, methyl ester
Common Name English
Eplerenone [WHO-DD]
Common Name English
SC-6611O
Code English
EPLERENONE [MART.]
Common Name English
EPLERENONE [USP-RS]
Common Name English
EPLERENONE [HSDB]
Common Name English
EPLERENONE [USAN]
Common Name English
Classification Tree Code System Code
WHO-VATC QC03DA04
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
LIVERTOX NBK547930
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
NCI_THESAURUS C270
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
WHO-ATC C03DA04
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
NDF-RT N0000175557
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
NDF-RT N0000011310
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
NCI_THESAURUS C843
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
Code System Code Type Description
EVMPD
SUB06574MIG
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
PUBCHEM
443872
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
INN
7596
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
WIKIPEDIA
EPLERENONE
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
USAN
II-52
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
DRUG CENTRAL
1032
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
RS_ITEM_NUM
1237553
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
ChEMBL
CHEMBL1095097
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
EPA CompTox
DTXSID2046094
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
IUPHAR
2876
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
RXCUI
298869
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY RxNorm
MERCK INDEX
M4951
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY Merck Index
HSDB
7522
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
CHEBI
31547
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
MESH
C414690
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
DAILYMED
6995V82D0B
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
DRUG BANK
DB00700
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
FDA UNII
6995V82D0B
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
CAS
107724-20-9
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY
NCI_THESAURUS
C47513
Created by admin on Fri Dec 16 18:34:57 UTC 2022 , Edited by admin on Fri Dec 16 18:34:57 UTC 2022
PRIMARY