Eplerenone

Eplerenone
Clinical data
Pronunciation	/ɛpˈlɛrənoʊn/
Trade names	Inspra, others
Other names	SC-66110; CGP-30083; 9-11α-Epoxymexrenone; 9,11α-Epoxy-7α-methoxycarbonyl-3-oxo-17α-pregn-4-ene-21,17-carbolactone
AHFS/Drugs.com	Monograph
MedlinePlus	a603004
License data	US DailyMed: Eplerenone;
Pregnancy; category	AU: B3;
Routes of; administration	By mouth (tablets)
ATC code	C03DA04 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	~70%
Protein binding	~50% (33–60%) (primarily to α1-acid glycoprotein)
Metabolism	Liver (CYP3A4)
Metabolites	6β-OH-EPL, 6β,21-OH-EPL, 21-OH-EPL, 3α,6β-OH-EPL (All inactive)
Elimination half-life	4–6 hours
Excretion	Urine (67%), feces (32%)
Identifiers
	IUPAC name methyl (4aS,4bR,5aR,6aS,7R,9aS,9bR,10R)-4a,6a-dimethyl-2,5'-dioxo-2,4,4',4a,5',5a,6,6a,8,9,9a,9b,10,11-tetradecahydro-3H,3'H-spiro[cyclopenta[7,8]phenanthro[4b,5-b]oxirene-7,2'-furan]-10-carboxylate;
CAS Number	107724-20-9 ;
PubChem CID	5282131;
IUPHAR/BPS	2876;
DrugBank	DB00700 ;
ChemSpider	10203511 ;
UNII	6995V82D0B;
KEGG	D01115 ;
ChEBI	CHEBI:31547 ;
ChEMBL	ChEMBL1095097 ;
PDB ligand	YNU (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID2046094 ;
ECHA InfoCard	100.106.615
Chemical and physical data
Formula	C24H30O6
Molar mass	414.498 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES COC(=O)[C@@H]4C\C1=C\C(=O)CC[C@]1(C)[C@@]65O[C@@H]6C[C@@]3(C)[C@@H](CC[C@]23CCC(=O)O2)[C@H]45;
	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 ; Key:JUKPWJGBANNWMW-VWBFHTRKSA-N ;
	(verify)

Eplerenone, marketed under brand name Inspa or Espler, is an aldosterone antagonist used primarily in the treatment of heart failure with reduced ejection fraction (HFrEF), particularly following myocardial infarction.^[5]^[6] It may also be considered as an add-on therapy in resistant hypertension;^[7] however, the majority of evidence in this setting supports the use of spironolactone (another drug in a same class), with fewer studies directly evaluating eplerenone.^[8]

It is also a steroidal antimineralocorticoid of the spirolactone group and a selective aldosterone receptor antagonist (SARA).^[9]

^ ^a ^b ^c ^d ^e Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 743–. ISBN 978-1-60913-345-0.
^ ^a ^b Sica DA (January 2005). "Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis". Heart Failure Reviews. 10 (1): 23–29. doi:10.1007/s10741-005-2345-1. PMID 15947888. S2CID 21437788.
^ Struthers A, Krum H, Williams GH (April 2008). "A comparison of the aldosterone-blocking agents eplerenone and spironolactone". Clinical Cardiology. 31 (4): 153–158. doi:10.1002/clc.20324. PMC 6652937. PMID 18404673.
^ Frishman WH, Cheng-Lai A, Nawarskas J (4 January 2005). Current Cardiovascular Drugs. Springer Science & Business Media. pp. 246–. ISBN 978-1-57340-221-7.
^ Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, et al. (3 April 2003). "Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction". New England Journal of Medicine. 348 (14): 1309–1321. doi:10.1056/NEJMoa030207. ISSN 0028-4793. PMID 12668699.
^ McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, et al. (6 January 2011). "Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms". New England Journal of Medicine. 364 (1): 11–21. doi:10.1056/NEJMoa1009492. ISSN 0028-4793. PMID 21073363.
^ Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, Egan BM, et al. (November 2018). "Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association". Hypertension. 72 (5): e53 – e90. doi:10.1161/HYP.0000000000000084. PMC 6530990. PMID 30354828.
^ Kunwar S, Rijal J, Alqatahni F, Panta R, Ishak N, Russell RP, et al. (November 2015). "The Effects of Aldosterone Antagonists in Patients With Resistant Hypertension: A Meta-Analysis of Randomized and Nonrandomized Studies". American Journal of Hypertension. 28 (11): 1376–1385. doi:10.1093/ajh/hpv031. ISSN 0895-7061. PMID 25801902.
^ Delyani JA, Rocha R, Cook CS, Tobert DS, Levin S, Roniker B, et al. (2001). "Eplerenone: a selective aldosterone receptor antagonist (SARA)". Cardiovascular Drug Reviews. 19 (3): 185–200. doi:10.1111/j.1527-3466.2001.tb00064.x. PMID 11607037.

[Lemke_2012-1] Lemke TL, Williams DA (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 743–. ISBN 978-1-60913-345-0.

[Sica_2005-2] Sica DA (January 2005). "Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis". Heart Failure Reviews. 10 (1): 23–29. doi:10.1007/s10741-005-2345-1. PMID 15947888. S2CID 21437788.

[Struthers_2008a-3] Struthers A, Krum H, Williams GH (April 2008). "A comparison of the aldosterone-blocking agents eplerenone and spironolactone". Clinical Cardiology. 31 (4): 153–158. doi:10.1002/clc.20324. PMC 6652937. PMID 18404673.

[Frishman_2005-4] Frishman WH, Cheng-Lai A, Nawarskas J (4 January 2005). Current Cardiovascular Drugs. Springer Science & Business Media. pp. 246–. ISBN 978-1-57340-221-7.

[5] Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, et al. (3 April 2003). "Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction". New England Journal of Medicine. 348 (14): 1309–1321. doi:10.1056/NEJMoa030207. ISSN 0028-4793. PMID 12668699.

[6] McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, et al. (6 January 2011). "Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms". New England Journal of Medicine. 364 (1): 11–21. doi:10.1056/NEJMoa1009492. ISSN 0028-4793. PMID 21073363.

[7] Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, Egan BM, et al. (November 2018). "Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association". Hypertension. 72 (5): e53 – e90. doi:10.1161/HYP.0000000000000084. PMC 6530990. PMID 30354828.

[8] Kunwar S, Rijal J, Alqatahni F, Panta R, Ishak N, Russell RP, et al. (November 2015). "The Effects of Aldosterone Antagonists in Patients With Resistant Hypertension: A Meta-Analysis of Randomized and Nonrandomized Studies". American Journal of Hypertension. 28 (11): 1376–1385. doi:10.1093/ajh/hpv031. ISSN 0895-7061. PMID 25801902.

[Delyani_2001-9] Delyani JA, Rocha R, Cook CS, Tobert DS, Levin S, Roniker B, et al. (2001). "Eplerenone: a selective aldosterone receptor antagonist (SARA)". Cardiovascular Drug Reviews. 19 (3): 185–200. doi:10.1111/j.1527-3466.2001.tb00064.x. PMID 11607037.

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