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By modifying the alternative drug Spironolactone, the new drug was developed in part to avoid undesired androgenic side effects in male patients.

Eplerenone was developed by Pharmacia Corporation, which was acquired by Pfizer in 2002. It was marketed by Pfizer under the trade name Inspra. The US Food and Drug Administration (FDA) approved the drug for sale in the United States in 2002. Relative to dosage, eplerenone costs an estimated $2.93 per day when treating congestive heart failure and $5.86 per day when treating hypertension.

Medical uses

Heart Failure

A variant of the spirolactone group, Eplerenone was developed to contradict the depletion of essential potassium and magnesium levels that are common amongst other mineralocorticoid receptor antagonists. It is a more expensive alternative to spironolactone. The recommended dosage for Eplerenone treating heart failure is 25-50 mg/day, depending on the tolerance of the patient. According to a study comparing both aldosterone blocking agents, the efficacy of Eplerenone over Spironolactone is dependent upon each individual patient.

Hypertension

Eplerenone can be used individually or in combination with other medications to treat hypertension in patients. Dosage ranges from a once daily dose of 50 mg to twice daily 50 mg dosage (no more than 100 mg/day is recommended, as there is no benefit on blood pressure relief). In an 8 week trial with 417 patients with mild to moderate hypertension, Eplerenone significantly decreased systolic and diastolic blood pressure in a dose-dependent man over a dose range of 50, 100 and 400 milligrams per dose . Eplerenone effectively reduces blood pressure compared to agents such as spironolactone, enalapril, losartan and amlodipine, but it's effect on mortality is still generally unknown .

Differences Between Spironolactone and Eplerenone Clinical Results in Heart Failure

_{RALES = Randomized Aldactone Evaluation Study, EPHESUS = Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study}

Parameter	RALES	EPHESUS
Drug:	Spironolactone	Eplerenone
Patients enrolled (n)	1663	6632
Population/Inclusion Criteria	NYHA Class III at the time of Enrollment	NYHA Class I-IV
Target Dose	50 mg/d	50 mg/d
Mean Dose Achieved	26 mg/d	43.5 mg/d
Mean duration of follow-up	24 mo	16 mo
Diuretic	100%	60%

Pharmacology

Eplerenone is also referred to chemically as "Pregn-4-ene-7,21-dicarboxylic acid, 9,11-epoxy-17-

hydroxy-3-oxo, γ-lactone, methyl ester (7α, 11α,17α), was derived from spironolactone by the introduction of a 9α,11α-epoxy bridge and by substitution of the 17α-thoacetyl group of spironolactone with a carbomethoxy group". The drug controls high blood pressure by binding the aldosterone hormone to the mineralocorticoid receptor (MR) in epithelial tissues, such as the kidney. This helps to increase blood volume and regulate blood pressure. Eplerenone differs from Spironolactone in its extensive metabolism, with a short half-life and inactive metabolites.

The chemical structure of three potassium-sparing diuretics, Eplerenone, Spironolactone, and Canrenone.

Adverse effects

Adverse effects of aldosterone treatments occur in non-epithelial tissues, like the heart and brain, due to changes in water retention and excretion of sodium and potassium. This is because other antimineralocorticoids have structural elements of the progesterone molecule, causing progestogenic and antiandrogenic outcomes. In this aspect, Eplerenone would be preferable to many male patients seeking no sexual side effects.

See also

• Finerenone

References

Category:Antimineralocorticoids Category:Epoxides Category:Lactones Category:Pfizer products Category:Steroids