Identification

Name
Eplerenone
Accession Number
DB00700
Description

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 414.4914
Monoisotopic: 414.204238692
Chemical Formula
C24H30O6
Synonyms
  • Eplerenona
  • Eplerenone
  • Epoxymexrenone
External IDs
  • SC-66110
  • SC-6611O

Pharmacology

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.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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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.

TargetActionsOrganism
AMineralocorticoid receptor
antagonist
Humans
Absorption

The absolute bioavailability of eplerenone is unknown.

Volume of distribution
  • 43 to 90 L
Protein binding

50%

Metabolism

Eplerenone is metabolized primarily by CYP3A4, however, no active metabolites have been identified in human plasma.

Hover over products below to view reaction partners

Route of elimination
Not Available
Half-life

4-6 hours

Clearance
  • Apparent plasma cl=10 L/hr
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Eplerenone Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirEplerenone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbametapirThe serum concentration of Eplerenone can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Eplerenone can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Eplerenone can be decreased when combined with Acalabrutinib.
AcarboseEplerenone may increase the excretion rate of Acarbose which could result in a lower serum level and potentially a reduction in efficacy.
AcebutololThe risk or severity of hyperkalemia can be increased when Eplerenone is combined with Acebutolol.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Eplerenone.
AcemetacinThe therapeutic efficacy of Eplerenone can be decreased when used in combination with Acemetacin.
AcetaminophenEplerenone may increase the excretion rate of Acetaminophen which could result in a lower serum level and potentially a reduction in efficacy.
AcetyldigitoxinEplerenone may decrease the excretion rate of Acetyldigitoxin which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products. Grapefruit juice may increase the serum levels of eplerenone by 25% by inhibiting CYP3A4.
  • Take with or without food.

Products

Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
InspraTablet, film coated50 mg/1OralG.D. Searle LLC Division of Pfizer Inc2002-09-27Not applicableUs
InspraTablet25 mg/1OralRebel Distributors2002-09-27Not applicableUs
InspraTablet, film coated25 mg/1OralG.D. Searle LLC Division of Pfizer Inc2002-09-27Not applicableUs
InspraTablet50 mgOralUpjohn Canada Ulc2009-05-05Not applicableCanada
InspraTablet, film coated50 mg/1OralPhysicians Total Care, Inc.2004-04-142011-06-30Us
InspraTablet25 mgOralUpjohn Canada Ulc2009-05-08Not applicableCanada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-eplerenoneTabletOralApotex CorporationNot applicableNot applicableCanada
Apo-eplerenoneTabletOralApotex CorporationNot applicableNot applicableCanada
EplerenoneTablet, film coated50 mg/1OralGreenstone LLC2002-09-27Not applicableUs
EplerenoneTablet, film coated50 mg/1OralMylan Pharmaceuticals Inc.2017-10-03Not applicableUs
EplerenoneTablet25 mg/1OralApotex Corp2008-07-302019-03-31Us
EplerenoneTablet50 mg/1OralRebel Distributors2008-08-01Not applicableUs
EplerenoneTablet25 mg/1OralUpsher-Smith Laboratories, LLC2015-03-16Not applicableUs
EplerenoneTablet, film coated25 mg/1OralAmerican Health Packaging2019-05-01Not applicableUs
EplerenoneTablet, film coated50 mg/1OralBreckenridge Pharmaceutical, Inc.2018-09-18Not applicableUs
EplerenoneTablet, film coated25 mg/1OralMylan Pharmaceuticals Inc.2017-10-03Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
C03DA04 — Eplerenone
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as spironolactones and derivatives. These are steroid lactones with a structure based on the spironolactone skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid lactones
Direct Parent
Spironolactones and derivatives
Alternative Parents
Oxepanes / Cyclohexenones / Gamma butyrolactones / Dicarboxylic acids and derivatives / Tetrahydrofurans / Methyl esters / Oxacyclic compounds / Epoxides / Dialkyl ethers / Organic oxides
show 1 more
Substituents
Aliphatic heteropolycyclic compound / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Cyclic ketone / Cyclohexenone / Dialkyl ether / Dicarboxylic acid or derivatives / Ether / Gamma butyrolactone
show 13 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
3-oxo steroid, epoxide, methyl ester, gamma-lactone, oxaspiro compound, steroid acid ester (CHEBI:31547)

Chemical Identifiers

UNII
6995V82D0B
CAS number
107724-20-9
InChI Key
JUKPWJGBANNWMW-VWBFHTRKSA-N
InChI
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
IUPAC Name
methyl (1'R,2R,2'S,9'R,10'R,11'S,15'S,17'R)-2',15'-dimethyl-5,5'-dioxo-18'-oxaspiro[oxolane-2,14'-pentacyclo[8.8.0.0¹,¹⁷.0²,⁷.0¹¹,¹⁵]octadecan]-6'-ene-9'-carboxylate
SMILES
[H][C@@]12CC[C@@]3(CCC(=O)O3)[C@@]1(C)C[C@H]1O[C@@]11[C@@]2([H])[C@@H](CC2=CC(=O)CC[C@]12C)C(=O)OC

References

Synthesis Reference

Bhaskar Reddy Guntoori, Svetoslav S. Bratovanov, Mohamed Ibrahim Zaki, Elena Bejan, Stephen E. Horne, "Process for the preparation and purification of eplerenone." U.S. Patent US20080234478, issued September 25, 2008.

US20080234478
General References
Not Available
Human Metabolome Database
HMDB0014838
KEGG Drug
D01115
KEGG Compound
C12512
PubChem Compound
443872
PubChem Substance
46509053
ChemSpider
10203511
BindingDB
50318300
RxNav
298869
ChEBI
31547
ChEMBL
CHEMBL1095097
ZINC
ZINC000003985982
Therapeutic Targets Database
DAP000085
PharmGKB
PA164749044
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
YNU
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eplerenone
AHFS Codes
  • 24:32.20 — Mineralocorticoid (Aldosterone) Receptor Antagonists
PDB Entries
5mwy
FDA label
Download (136 KB)
MSDS
Download (68.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentChronic Central Serous Chorioretinopathy1
4CompletedBasic ScienceMetabolic Syndromes1
4CompletedBasic SciencePharmacodynamics1
4CompletedPreventionChronic Renal Failure (CRF)1
4CompletedPreventionMyocardial Infarction1
4CompletedTreatmentAtrial Switch Procedure / Transposition of the Great Vessels / Transposition of the Great Vessels With Atrial Switch1
4CompletedTreatmentChronic Central Serous Chorioretinopathy1
4CompletedTreatmentCongestive Heart Failure (CHF)1
4CompletedTreatmentCongestive Heart Failure (CHF) / Diastole1
4CompletedTreatmentHeart Failure / Left Ventricular Dysfunction1

Pharmacoeconomics

Manufacturers
  • Apotex inc
  • Sandoz inc
  • Gd searle llc
Packagers
  • Apotex Inc.
  • Eon Labs
  • GD Searle LLC
  • Greenstone LLC
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Sandoz
Dosage Forms
FormRouteStrength
Tablet, film coatedOral25 MG
Tablet, film coatedOral50 MG
TabletOral50 mg/1
TabletOral
TabletOral25 mg/1
TabletOral25 mg
TabletOral50 mg
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Prices
Unit descriptionCostUnit
Inspra 25 mg tablet4.87USD tablet
Inspra 50 mg tablet4.87USD tablet
Eplerenone 25 mg tablet4.18USD tablet
Eplerenone 50 mg tablet4.18USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6863902No2005-03-082020-10-10Us
US6410054Yes2002-06-252020-06-08Us
US6410524Yes2002-06-252020-05-05Us
US6495165Yes2002-12-172020-06-08Us
US6534093Yes2003-03-182020-06-08Us
US6558707Yes2003-05-062020-06-08Us
US6747020Yes2004-06-082020-05-05Us
US7157101Yes2007-01-022020-06-08Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySlightly solubleNot Available
logP1.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00903 mg/mLALOGPS
logP1.67ALOGPS
logP2.33ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)15.11ChemAxon
pKa (Strongest Basic)-4.2ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area82.2 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity106.68 m3·mol-1ChemAxon
Polarizability43.79 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9839
Blood Brain Barrier+0.8556
Caco-2 permeable+0.5076
P-glycoprotein substrateSubstrate0.7017
P-glycoprotein inhibitor IInhibitor0.8166
P-glycoprotein inhibitor IIInhibitor0.8066
Renal organic cation transporterNon-inhibitor0.7209
CYP450 2C9 substrateNon-substrate0.8229
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.6978
CYP450 2C9 inhibitorNon-inhibitor0.7982
CYP450 2D6 inhibitorNon-inhibitor0.931
CYP450 2C19 inhibitorNon-inhibitor0.839
CYP450 3A4 inhibitorNon-inhibitor0.8368
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8902
Ames testNon AMES toxic0.7496
CarcinogenicityNon-carcinogens0.9441
BiodegradationNot ready biodegradable0.9891
Rat acute toxicity2.4761 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9453
hERG inhibition (predictor II)Non-inhibitor0.7742
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates targ...
Gene Name
NR3C2
Uniprot ID
P08235
Uniprot Name
Mineralocorticoid receptor
Molecular Weight
107066.575 Da
References
  1. Moore TD, Nawarskas JJ, Anderson JR: Eplerenone: a selective aldosterone receptor antagonist for hypertension and heart failure. Heart Dis. 2003 Sep-Oct;5(5):354-63. [PubMed:14503934]
  2. Fraccarollo D, Galuppo P, Hildemann S, Christ M, Ertl G, Bauersachs J: Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction. J Am Coll Cardiol. 2003 Nov 5;42(9):1666-73. [PubMed:14607457]
  3. Rogerson FM, Yao Y, Smith BJ, Fuller PJ: Differences in the determinants of eplerenone, spironolactone and aldosterone binding to the mineralocorticoid receptor. Clin Exp Pharmacol Physiol. 2004 Oct;31(10):704-9. [PubMed:15554912]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Cook CS, Berry LM, Kim DH, Burton EG, Hribar JD, Zhang L: Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5. Drug Metab Dispos. 2002 Dec;30(12):1344-51. [PubMed:12433801]
  2. McGraw J, Cherney M, Bichler K, Gerhardt A, Nauman M: The Relative Role of CYP3A4 and CYP3A5 in Eplerenone Metabolism. Toxicol Lett. 2019 Aug 10. pii: S0378-4274(19)30218-8. doi: 10.1016/j.toxlet.2019.08.003. [PubMed:31408697]
  3. Eplenerone FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Cook CS, Berry LM, Kim DH, Burton EG, Hribar JD, Zhang L: Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5. Drug Metab Dispos. 2002 Dec;30(12):1344-51. [PubMed:12433801]
  2. McGraw J, Cherney M, Bichler K, Gerhardt A, Nauman M: The Relative Role of CYP3A4 and CYP3A5 in Eplerenone Metabolism. Toxicol Lett. 2019 Aug 10. pii: S0378-4274(19)30218-8. doi: 10.1016/j.toxlet.2019.08.003. [PubMed:31408697]
  3. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 11-beta-monooxygenase activity
Specific Function
Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Gene Name
CYP11B2
Uniprot ID
P19099
Uniprot Name
Cytochrome P450 11B2, mitochondrial
Molecular Weight
57559.62 Da
References
  1. Kobayashi N, Yoshida K, Nakano S, Ohno T, Honda T, Tsubokou Y, Matsuoka H: Cardioprotective mechanisms of eplerenone on cardiac performance and remodeling in failing rat hearts. Hypertension. 2006 Apr;47(4):671-9. doi: 10.1161/01.HYP.0000203148.42892.7a. Epub 2006 Feb 27. [PubMed:16505212]

Drug created on June 13, 2005 07:24 / Updated on August 10, 2020 08:11

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