eplerenone 抑制人盐皮质激素受体，IC50 值为 0.081 μM[2]。

在动脉粥样硬化载脂蛋白缺陷（EO）小鼠中，口服依普利酮（200 mg/kg/天）三个月可显着降低氧化应激和动脉粥样硬化的进展[3]。

Animal/Disease Models: Atherosclerotic apolipoprotein Edeficient (EO) mice[3]
Doses: 200 mg/kg
Route of Administration: po (oral gavage) 200 mg/kg/day for 3 months
Experimental Results: Dramatically diminished systolic and diastolic blood pressure by 12% and 11%, respectively. diminished serum susceptibility to lipid peroxidation by as much as 26%, and increased serum paraoxonase activity by 28%. decreased levels of lipid peroxides, and Dramatically decreased macrophage oxidation of low-density lipoprotein (LDL) and superoxide ion release. Dramatically decreased the atherosclerotic lesion area.

Absorption, Distribution and Excretion
The absolute bioavailability of eplerenone is unknown.
43 to 90 L
Apparent plasma cl=10 L/hr
Apparent plasma clearance: approximately 10 L/hr. Less than 5% is recovered as unchanged drug in the urine and feces. Renal: 67%. Fecal: 32%.
Mean peak plasma concentrations of eplerenone are reached approximately 1.5 hours following oral administration. The absolute bioavailability of eplerenone is unknown. Both peak plasma levels (Cmax) and area under the curve (AUC) are dose proportional for doses of 25 to 100 mg and less than proportional at doses above 100 mg. The plasma protein binding of eplerenone is about 50% and it is primarily bound to alpha 1-acid glycoproteins. The apparent volume of distribution at steady state ranged from 43 to 90 L. Eplerenone does not preferentially bind to red blood cells.
Eplerenone is distributed into milk in rats; ... .
... Preclinical data show that eplerenone and/or metabolites are present in rat breast milk (0.85:1 [milk:plasma] AUC ratio) obtained after a single oral dose. Peak concentrations in plasma and milk were obtained from 0.5 to 1 hour after dosing.

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Metabolism / Metabolites
Eplerenone is metabolized primarily by CYP3A4, however, no active metabolites have been identified in human plasma.
Eplerenone metabolism is primarily mediated via CYP3A4. No active metabolites have been identified in human plasma.
Eplerenone has known human metabolites that include 21-hydroxyeplerenone and 6beta-hydroxyeplerenone.

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Biological Half-Life
4-6 hours
Elimination: 4 to 6 hours.

Hepatotoxicity
Eplerenone therapy has been associated with a low rate of serum aminotransferase elevations which are typically mild and transient. ALT elevations of greater than 3 times the ULN occurred in 0.7% and greater than 5 times in 0.2% of eplerenone treated compared to 0.3% and 0.3% of placebo treated subjects. Idiosyncratic, clinically apparent liver injury from eplerenone has yet to be reported. The similarity in structure to spironolactone suggests that it may share susceptibility to the acute liver injury reported rarely with that agent.
Likelihood score: E* (unproven but suspect rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Data from one mother-infant pair indicate that eplerenone is poorly excreted into breastmilk. Until more data are available, eplerenone should be used with careful infant monitoring during breastfeeding.
◉ Effects in Breastfed Infants
A woman with primary aldosteronism was receiving eplerenone 50 mg once daily (0.79 mg/kg daily) during pregnancy and postpartum. Her infant was partially breastfed for 3 months, with over 50% of nutrition from breastmilk. The infant developed normally and had no detectable adverse drug effects at the 1- or 3-month checkups.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
50%

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Interactions
Lithium toxicity has been reported in patients receiving lithium concomitantly with diuretics and ACE inhibitors; serum lithium concentrations should be monitored if eplerenone is administered concomitantly with lithium.
Antihypertensive and/or diuretic effects may be potentiated when these medications /other hypotension-producing medications/ are used concurrently with eplerenone; although some antihypertensive and/or diuretic combinations are frequently used for therapeutic advantage, dosage adjustments may be necessary during concurrent use.
/Use of grapefruit juice with eplerenone/ may cause a small increase in exposure.
Concomitant use of potent inhibitors of CYP450 3A4 /including eltraconazole or ketoconazole/ with eplerenone is contraindicated.
For more Interactions (Complete) data for EPLERENONE (12 total), please visit the HSDB record page.

[1]. Myron H Weinberger, et al. Eplerenone, a selective aldosterone blocker, in mild-to-moderate hypertension. Am J Hypertens. 2002 Aug;15(8):709-16.
[2]. Dhillon, S., Eplerenone: a review of its use in patients with chronic systolic heart failure and mild symptoms. Drugs, 2013. 73(13): p. 1451-62.
[3]. Shlomo Keidar, et al. Effect of eplerenone, a selective aldosterone blocker, on blood pressure, serum and macrophage oxidative stress, and atherosclerosis in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol. 2003 Jun;41(6):955-63.

Eplerenone is a steroid acid ester, a methyl ester, an oxaspiro compound, a gamma-lactone, an organic heteropentacyclic compound, a 3-oxo-Delta(4) steroid and an epoxy steroid. It has a role as an aldosterone antagonist and an antihypertensive agent. It derives from a hydride of a pregnane.
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 is an Aldosterone Antagonist. The mechanism of action of eplerenone is as an Aldosterone Antagonist.
Eplerenone is an aldosterone receptor antagonist and potassium-sparing diuretic used in the therapy of hypertension. Eplerenone therapy has been associated with transient elevations in serum aminotransferase levels, but has yet to be linked to cases of clinically apparent drug induced liver disease.
Eplerenone is a selective aldosterone receptor antagonist. Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, thereby decreasing sodium resorption and subsequently increasing water outflow. This leads to a decrease in blood pressure. Eplerenone is used in the treatment of hypertension and congestive heart failure.
A spironolactone derivative and selective ALDOSTERONE RECEPTOR antagonist that is used in the management of HYPERTENSION and CONGESTIVE HEART FAILURE, post-MYOCARDIAL INFARCTION.

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Drug 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.
FDA Label

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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.
Eplerenone has relative selectivity in binding to recombinant human mineralocorticoid receptors compared to its binding to recombinant human glucocorticoid, progesterone, and androgen receptors.
Eplerenone has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with the inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulation levels do not overcome the effect of eplerenone on blood pressure.
Eplerenone binds to the mineralocorticoid receptor and blocks the binding of aldosterone, a component of the renin-angiotensin-aldosterone-system (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, brain) tissues and increases blood pressure through induction of sodium resorption and possibly other mechanisms.

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Therapeutic Uses
Eplerenone is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive drugs. /Included in US product labeling/
Inspra is indicated to improve survival of stable patients with left ventricular systolic dysfunction (ejection fraction less than or equal to 40%) and clinical evidence of congestive heart failure after an acute myocardial infarction.
... Eplerenone should replace spironolactone as a natriuretic and antikaliuretic in heart failure and as add-on treatment in severe systolic cardiac insufficiency, and it is indicated after an acute myocardial infarction complicated by left ventricular dysfunction and heart failure. The finding that hypertension control with diuretic-based pharmacotherapy results in better prevention of heart failure than pressure reduction with other drugs makes it pertinent to investigate whether diuretics in general, and eplerenone in particular, should constitute part of the initial pharmacotherapy for heart failure when there is no overt fluid retention and independent of the etiology. ...

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Drug Warnings
FDA Pregnancy Risk Category: B /NO EVIDENCE OF RISK IN HUMANS. Adequate, well controlled studies in pregnant women have not shown increased risk of fetal abnormalities despite adverse findings in animals, or, in the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote but remains a possibility./
... When used for hypertension, the drug is contraindicated in patients with type 2 diabetes mellitus with microalbuminuria, serum creatinine concentrations exceeding 2 or 1.8 mg/dL in males or females, respectively, creatinine clearance less than 50 mL/minute, ... .
The most serious risk associated with eplerenone therapy is hyperkalemia (serum potassium greater than 5.5 mEq/L), which may cause serious, sometimes fatal, cardiac arrhythmias. Patients with impaired renal function or diabetes mellitus and patients receiving concurrent agents affecting the renin-angiotensin-aldosterone system (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists) are at an increased risk for developing hyperkalemia. Eplerenone should be used with caution in patients with congestive heart failure following an acute myocardial infarction, who have renal impairment (i.e., serum creatinine concentrations exceeding 2 or 1.8 mg/dL in males or females, respectively, or creatinine clearance of 50 mL/minute or less) or those with diabetes mellitus (including those with proteinuria). Serum potassium concentrations should be monitored periodically in patients receiving eplerenone. Dosage reduction has been shown to decrease serum potassium concentrations.
Adverse effects reported in 1% or more of patients receiving eplerenone for the management of hypertension are dizziness, fatigue, flu-like symptoms, cough, diarrhea, abdominal pain, hyperkalemia, decreased serum sodium concentrations, abnormal vaginal bleeding, gynecomastia, hypercholesterolemia, hypertriglyceridemia, mastodynia, or albuminuria.
For more Drug Warnings (Complete) data for EPLERENONE (12 total), please visit the HSDB record page.

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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.

C24H30O6

414.49

414.204

107724-20-9

Eplerenone-d3

443872

White to off-white solid powder

1.3±0.1 g/cm3

597.9±50.0 °C at 760 mmHg

241-243ºC

259.5±30.2 °C

0.0±1.7 mmHg at 25°C

1.587

1.05

82.2

0

6

2

30

907

8

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

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

methyl (1R,2S,9R,10R,11S,14R,15S,17R)-2,15-dimethyl-5,5'-dioxospiro[18-oxapentacyclo[8.8.0.01,17.02,7.011,15]octadec-6-ene-14,2'-oxolane]-9-carboxylate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.03 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.03 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (6.03 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。