Identification

Name
Eplerenone
Accession Number
DB00700  (APRD00707)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • Eplerenona
  • Epoxymexrenone
External IDs
SC-66110 / SC-6611O
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
InspraTablet, film coated50 mg/1OralPhysicians Total Care, Inc.2004-04-142011-06-30Us
InspraTablet25 mgOralPfizer2009-05-08Not applicableCanada
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 mgOralPfizer2009-05-05Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-eplerenoneTablet50 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-eplerenoneTablet25 mgOralApotex CorporationNot applicableNot applicableCanada
EplerenoneTablet, film coated25 mg/1OralGreenstone, Llc2002-09-27Not applicableUs
EplerenoneTablet25 mg/1OralAmerincan Health Packaging2015-08-24Not applicableUs
EplerenoneTablet25 mg/1OralApotex Corporation2008-07-30Not applicableUs
EplerenoneTablet, film coated50 mg/1OralAccord Healthcare, Inc.2018-10-09Not applicableUs
EplerenoneTablet, film coated25 mg/1OralAvera McKennan Hospital2015-06-172018-06-07Us
EplerenoneTablet, film coated25 mg/1OralBreckenridge Pharmaceutical, Inc.2018-09-18Not applicableUs
EplerenoneTablet50 mg/1OralUpsher-Smith Laboratories, LLC2015-03-16Not applicableUs
EplerenoneTablet50 mg/1OralEon Labs, Inc.2008-08-01Not applicableUs
Categories
UNII
6995V82D0B
CAS number
107724-20-9
Weight
Average: 414.4914
Monoisotopic: 414.204238692
Chemical Formula
C24H30O6
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

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
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
Human
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.

Route of elimination
Not Available
Half life

4-6 hours

Clearance
  • Apparent plasma cl=10 L/hr
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
DrugInteraction
(R)-warfarinThe metabolism of Eplerenone can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Eplerenone can be decreased when combined with (S)-Warfarin.
3,5-diiodothyropropionic acidThe metabolism of Eplerenone can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Eplerenone.
5-androstenedioneThe metabolism of Eplerenone can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Eplerenone can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of Eplerenone can be decreased when combined with 6-O-benzylguanine.
AbacavirEplerenone may increase the excretion rate of Abacavir which could result in a lower serum level and potentially a reduction in efficacy.
AbemaciclibThe metabolism of Eplerenone can be decreased when combined with Abemaciclib.
AbirateroneThe metabolism of Eplerenone can be decreased when combined with Abiraterone.
Food Interactions
Not Available

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
External Links
Human Metabolome Database
HMDB0014838
KEGG Drug
D01115
KEGG Compound
C12512
PubChem Compound
443872
PubChem Substance
46509053
ChemSpider
10203511
BindingDB
50318300
ChEBI
31547
ChEMBL
CHEMBL1095097
Therapeutic Targets Database
DAP000085
PharmGKB
PA164749044
IUPHAR
2876
Guide to Pharmacology
GtP Drug Page
HET
YNU
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Eplerenone
ATC Codes
C03DA04 — 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
1CompletedNot AvailableChronic Kidney Disease (CKD)1
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailablePharmacology, Clinical1
1CompletedBasic ScienceHealthy Volunteers / Pharmacodynamics1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1Not Yet RecruitingScreeningType 2 Diabetes Mellitus1
1RecruitingNot AvailableHealthy Volunteers1
1RecruitingTreatmentDiabetic Nephropathies1
1WithdrawnOtherFasting / Healthy Volunteers / Pharmacokinetics1
1WithdrawnOtherHealthy Volunteers1
1, 2CompletedTreatmentGitelman's syndrome1
1, 2RecruitingTreatmentCKD II-III1
2CompletedTreatmentCentral Serous Chorioretinopathy (CSC)1
2CompletedTreatmentChronic Kidney Disease (CKD)1
2CompletedTreatmentDiabetic Nephropathies1
2CompletedTreatmentHeart Failure, Unspecified2
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentHypertension,Essential2
2TerminatedPreventionNonvalvular Atrial Fibrillation1
2TerminatedTreatmentCardiac Steatosis / Hepatic Steatosis1
2TerminatedTreatmentHigh Blood Pressure (Hypertension)2
2Unknown StatusTreatmentCentral Serous Chorioretinopathy (CSC)1
2Unknown StatusTreatmentKidney Insufficiency, Chronic / Transplantation, Kidney1
2WithdrawnTreatmentAscites / Liver Cirrhosis1
2, 3Not Yet RecruitingTreatmentCentral Serous Chorioretinopathy (CSC)1
2, 3RecruitingTreatmentPrimary Hyperparathyroidism1
2, 3TerminatedPreventionCancer, Breast1
3Active Not RecruitingTreatmentGlucose tolerance impaired / Heart Failure, Unspecified / Type 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentHypertension,Essential1
3Active Not RecruitingTreatmentPhospholamban R14del Mutation-related Cardiomyopathy1
3CompletedPreventionEndothelial Dysfunction / Metabolic Syndromes1
3CompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
3CompletedTreatmentHeart Failure, Unspecified2
3CompletedTreatmentHigh Blood Pressure (Hypertension)2
3CompletedTreatmentHypertension,Essential1
3RecruitingTreatmentEnd-Stage Renal Disease (ESRD)1
3TerminatedTreatmentChronic Kidney Disease (CKD)1
4CompletedBasic SciencePharmacodynamics1
4CompletedPreventionChronic Renal Failure (CRF)1
4CompletedPreventionHigh Blood Pressure (Hypertension)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, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)1
4CompletedTreatmentIschaemic Heart Diseases1
4CompletedTreatmentMyocardial Infarction1
4CompletedTreatmentType 2 Diabetes Mellitus1
4RecruitingBasic ScienceAbdominal Obesity Metabolic Syndrome / High Blood Pressure (Hypertension) / Insulin Resistance1
4RecruitingTreatmentAortic Aneurysm, Abdominal1
4RecruitingTreatmentBack Pain Lower Back / Degenerative Intervertebral Discs / Sciatic Radiculopathy1
4RecruitingTreatmentChronic Central Serous Chorioretinopathy1
4TerminatedPreventionMetabolic Syndromes1
4TerminatedTreatmentDiastolic Heart Failure1
4TerminatedTreatmentSingle Ventricle With a Fontan Palliation / Tetralogy Of Fallot / Transposition of the Great Vessels With an Arterial Switch1
4Unknown StatusDiagnosticDialysis therapy / High Blood Pressure (Hypertension) / Hyperaldosteronism1
4Unknown StatusSupportive CareMetabolic Syndromes1
4Unknown StatusTreatmentHypertensive Left Ventricular Hypertrophy1
4Unknown StatusTreatmentProphylaxis of cardiomyopathy1
4WithdrawnTreatmentChronic Kidney Disease (CKD) / High Blood Pressure (Hypertension)1
4WithdrawnTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)1
Not AvailableCompletedBasic ScienceHypoglycemia1
Not AvailableCompletedPreventionSystemic Proinflammatory State1
Not AvailableCompletedTreatmentAlbuminuria / Diabetes Mellitus (DM) / Endothelial Dysfunction1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentCentral Serous Chorioretinopathy (CSC)1
Not AvailableCompletedTreatmentDiastolic Heart Failure1
Not AvailableCompletedTreatmentDuchenne's Muscular Dystrophy (DMD)1
Not AvailableCompletedTreatmentEnd Stage Renal Disease (ESRD) / Hemodialysis Treatment1
Not AvailableCompletedTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableCompletedTreatmentIschemia-Reperfusion Injury1
Not AvailableRecruitingNot AvailableChronic Heart Failure (CHF)1
Not AvailableRecruitingBasic ScienceEndothelial Dysfunction / Insulin Resistance1
Not AvailableRecruitingBasic SciencePrimary Aldosteronism1
Not AvailableRecruitingDiagnosticHigh Blood Pressure (Hypertension)1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableTerminatedPreventionMyocardial Remodeling1
Not AvailableUnknown StatusScreeningHigh Blood Pressure (Hypertension) / Hyperaldosteronism1

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
TabletOral50 mg/1
Tablet, film coatedOral25 mg/1
TabletOral25 mg
TabletOral50 mg
TabletOral25 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)
US6863902No2000-10-102020-10-10Us
US6410054Yes2000-06-082020-06-08Us
US6410524Yes2000-05-052020-05-05Us
US6495165Yes2000-06-082020-06-08Us
US6534093Yes2000-06-082020-06-08Us
US6558707Yes2000-06-082020-06-08Us
US6747020Yes2000-05-052020-05-05Us
US7157101Yes2000-06-082020-06-08Us

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

Taxonomy

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
Spironolactone / Cyclohexenone / Oxepane / Dicarboxylic acid or derivatives / Gamma butyrolactone / Tetrahydrofuran / Methyl ester / Carboxylic acid ester / Ketone / Lactone
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)

Targets

Kind
Protein
Organism
Human
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
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 14, 2018 12:45