Icosapent ethyl

Identification

Name
Icosapent ethyl
Accession Number
DB08887  (DB06291)
Type
Small Molecule
Groups
Approved, Investigational, Nutraceutical
Description

Icosapent ethyl or ethyl eicosapentaenoic acid is a synthetic derivative of the omega-3 fatty acid eicosapentaenoic acid (EPA). It is used as adjunct therapy for severe hypertriglyceridemia (TG levels > 500 mg/dL). FDA approved on July 26, 2012.

Structure
Thumb
Synonyms
  • (all-Z)-5,8,11,14,17-Eicosapentaenoic acid ethyl ester
  • all-cis-ethyl 5,8,11,14,17-icosapentaenoate
  • cis-Eicosapentaenoic acid ethyl ester
  • E-EPA
  • Eicosapentaenoic acid ethyl ester
  • ethyl (5Z,8Z,11Z,14Z,17Z)-eicosa-5,8,11,14,17-pentaenoate
  • ethyl (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate
  • ethyl (5Z,8Z,11Z,14Z,17Z)-icosapentaenoate
  • Ethyl (all cis)-5,8,11,14,17-icosapentaenoate
  • Ethyl all-cis-5,8,11,14,17-icosapentaenoate
  • Ethyl Eicosapentaenoate
  • Ethyl icosapentate
  • Ethyl-Eicosapentaenoic Acid
  • Ethyl-EPA
  • Timnodonic acid ethyl ester
External IDs
AMR 101 / AMR-101 / AMR101
Active Moieties
NameKindUNIICASInChI Key
IcosapentunknownAAN7QOV9EA10417-94-4JAZBEHYOTPTENJ-JLNKQSITSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
VascepaCapsule1000 mg/1OralAmarin Pharma Inc.2012-10-01Not applicableUs
VascepaCapsule500 mg/1OralAmarin Pharma Inc.2016-09-16Not applicableUs
VascepaCapsule1000 mg/1OralAmarin Pharma Inc.2012-10-01Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Vp-pnv-dhaIcosapent ethyl (15.8 mg/1) + Ascorbic acid (80 mg/1) + Calcium Carbonate (50 mg/1) + Cholecalciferol (400 [iU]/1) + Cupric sulfate pentahydrate (1 mg/1) + Cyanocobalamin (12 ug/1) + Doconexent (200 mg/1) + Ferrous fumarate (28 mg/1) + Folic Acid (1 mg/1) + Magnesium oxide (30 mg/1) + Niacin (20 mg/1) + Pyridoxine (16 mg/1) + Riboflavin (2.2 mg/1) + Thiamine mononitrate (6 mg/1) + Vitamin A palmitate (2500 [iU]/1) + Vitamin E (30 [iU]/1) + Zinc oxide (20 mg/1)Capsule, gelatin coatedOralVirtus Pharmaceuticals2012-04-012012-08-22Us
International/Other Brands
Epadel
Categories
UNII
6GC8A4PAYH
CAS number
86227-47-6
Weight
Average: 330.5042
Monoisotopic: 330.255880332
Chemical Formula
C22H34O2
InChI Key
SSQPWTVBQMWLSZ-AAQCHOMXSA-N
InChI
InChI=1S/C22H34O2/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)24-4-2/h5-6,8-9,11-12,14-15,17-18H,3-4,7,10,13,16,19-21H2,1-2H3/b6-5-,9-8-,12-11-,15-14-,18-17-
IUPAC Name
ethyl (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoate
SMILES
CCOC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC

Pharmacology

Indication

Icosapent ethyl is used as adjunct therapy to reduce triglyceride (TG) levels in adults with severe (>500 mg/dL) hypertriglyceridemia.

Associated Conditions
Pharmacodynamics
Not Available
Mechanism of action

Studies suggest that EPA reduces hepatic very low-density lipoprotein triglycerides (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.

Absorption

Icosapent ethyl is de-esterfied, converted into active EPA, and then absorbed in the small intestine. It reaches peak plasma concentration in 5 hours post-oral administration. Very little (<1%) is left circulating in the plasma as EPA incorporates into phospholipids, TG's, and cholesteryl esters.

Volume of distribution

Steady state volume of distribution of active EPA is 88 L

Protein binding
Not Available
Metabolism

Once converted into active EPA, it is hepatically metabolized into acetyl Coenzyme A via beta-oxidation.

Route of elimination

Icosapent ethyl is not renally excreted

Half life

The half life of EPA is 89 hours.

Clearance

Total plasma clearance, EPA = 684 mL/hr

Toxicity

Icosapent ethyl is generally well tolerated and adverse effects are unrelated to treatment.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabIcosapent ethyl may increase the anticoagulant activities of Abciximab.
AcenocoumarolThe risk or severity of bleeding can be increased when Icosapent ethyl is combined with Acenocoumarol.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Icosapent ethyl is combined with Acetylsalicylic acid.
AloxiprinThe risk or severity of adverse effects can be increased when Icosapent ethyl is combined with Aloxiprin.
AlteplaseIcosapent ethyl may increase the anticoagulant activities of Alteplase.
Aminosalicylic AcidThe risk or severity of adverse effects can be increased when Icosapent ethyl is combined with Aminosalicylic Acid.
AnagrelideIcosapent ethyl may increase the anticoagulant activities of Anagrelide.
AncrodIcosapent ethyl may increase the anticoagulant activities of Ancrod.
AndrographolideAndrographolide may increase the antiplatelet activities of Icosapent ethyl.
AnistreplaseIcosapent ethyl may increase the anticoagulant activities of Anistreplase.
Food Interactions
Not Available

References

General References
  1. Ballantyne CM, Braeckman RA, Soni PN: Icosapent ethyl for the treatment of hypertriglyceridemia. Expert Opin Pharmacother. 2013 Jul;14(10):1409-16. doi: 10.1517/14656566.2013.798645. Epub 2013 May 24. [PubMed:23701295]
External Links
Human Metabolome Database
HMDB0039530
KEGG Drug
D01892
KEGG Compound
C16184
PubChem Compound
9831415
PubChem Substance
175427134
ChemSpider
8007147
ChEBI
80366
ChEMBL
CHEMBL2095209
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ethyl_eicosapentaenoic_acid
FDA label
Download (275 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHypertriglyceridemias1
1Unknown StatusTreatmentDiabetes Mellitus, Non-Insulin-Dependent / Hypertriglyceridemias1
2Not Yet RecruitingTreatmentMalignant Neoplasm of Colon1
2RecruitingSupportive CareAdvanced Malignant Neoplasm / Malignant Neoplasms of Independent (Primary) Multiple Sites / Metastatic Colorectal Cancers / Tiredness1
2, 3CompletedTreatmentPsychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorders1
2, 3CompletedTreatmentSchizophrenia Prodrome1
2, 3RecruitingPreventionAlzheimer's Disease (AD)1
3Active Not RecruitingPreventionCardiovascular Disease (CVD)1
3CompletedTreatmentDepression / Depressive Disorders1
3CompletedTreatmentHuntington's Disease (HD)1
3CompletedTreatmentHypertriglyceridemias2
3RecruitingPreventionLiver Metastasis / Malignant Neoplasm of Colon1
3TerminatedPreventionCoronary Artery Disease / Type 2 Diabetes Mellitus1
4CompletedPreventionCerebral Vasospasm / Subarachnoid Hemorrhage1
4CompletedPreventionMyocardial Infarction, Unstable Angina Pectoris, Sudden Cardiac Death, Stroke, Peripheral Artery Disease1
Not AvailableRecruitingTreatmentHypertriglyceridemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral1000 mg/1
CapsuleOral500 mg/1
Capsule, gelatin coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8293727No2010-02-092030-02-09Us
US8293728No2010-02-092030-02-09Us
US8314086No2010-02-092030-02-09Us
US8318715No2010-02-092030-02-09Us
US8357677No2010-02-092030-02-09Us
US8367652No2010-02-092030-02-09Us
US8377920No2010-02-092030-02-09Us
US8399446No2010-02-092030-02-09Us
US8415335No2010-02-092030-02-09Us
US8426399No2010-02-092030-02-09Us
US8431560No2010-02-092030-02-09Us
US8440650No2010-02-092030-02-09Us
US8445003No2010-04-292030-04-29Us
US8445013No2010-04-292030-04-29Us
US8501225No2010-04-292030-04-29Us
US8524698No2010-04-292030-04-29Us
US8551521No2010-04-292030-04-29Us
US8563608No2010-04-292030-04-29Us
US8617593No2010-04-292030-04-29Us
US8546372No2010-04-292030-04-29Us
US8518929No2010-04-292030-04-29Us
US8617594No2010-04-292030-04-29Us
US8623406No2010-04-292030-04-29Us
US8298554No2010-04-292030-04-29Us
US8188146No2000-01-272020-01-27Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.83e-05 mg/mLALOGPS
logP6.8ALOGPS
logP6.73ChemAxon
logS-6.5ALOGPS
pKa (Strongest Basic)-7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area26.3 Å2ChemAxon
Rotatable Bond Count15ChemAxon
Refractivity110.59 m3·mol-1ChemAxon
Polarizability40.32 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9947
Blood Brain Barrier+0.9783
Caco-2 permeable+0.7651
P-glycoprotein substrateNon-substrate0.7486
P-glycoprotein inhibitor INon-inhibitor0.8803
P-glycoprotein inhibitor IINon-inhibitor0.812
Renal organic cation transporterNon-inhibitor0.8776
CYP450 2C9 substrateNon-substrate0.8606
CYP450 2D6 substrateNon-substrate0.9069
CYP450 3A4 substrateNon-substrate0.625
CYP450 1A2 substrateNon-inhibitor0.5469
CYP450 2C9 inhibitorNon-inhibitor0.9392
CYP450 2D6 inhibitorNon-inhibitor0.9277
CYP450 2C19 inhibitorNon-inhibitor0.9562
CYP450 3A4 inhibitorNon-inhibitor0.9476
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6856
Ames testNon AMES toxic0.6329
CarcinogenicityCarcinogens 0.5714
BiodegradationReady biodegradable0.8556
Rat acute toxicity1.3874 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8771
hERG inhibition (predictor II)Non-inhibitor0.897
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 fatty acid esters. These are carboxylic ester derivatives of a fatty acid.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acid esters
Direct Parent
Fatty acid esters
Alternative Parents
Carboxylic acid esters / Monocarboxylic acids and derivatives / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Fatty acid ester / Carboxylic acid ester / Monocarboxylic acid or derivatives / Carboxylic acid derivative / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organooxygen compound / Carbonyl group / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
long-chain fatty acid ethyl ester (CHEBI:84883)

Drug created on May 28, 2013 14:35 / Updated on October 01, 2018 14:43