Identification
- Summary
Epoprostenol is a vasodilator and platelet aggregation inhibitor used for the management of primary pulmonary hypertension and pulmonary hypertension in patients with heart failure.
- Brand Names
- Flolan, Veletri
- Generic Name
- Epoprostenol
- DrugBank Accession Number
- DB01240
- Background
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Epoprostenol (DB01240)
- Weight
- Average: 352.4651
Monoisotopic: 352.224974134 - Chemical Formula
- C20H32O5
- Synonyms
- (5Z,13E)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
- (5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid
- Epoprostenol
- PGI2
- PGX
- Prostacyclin
- Prostaglandin I2
- Prostaglandin X
- Vasocyclin
- External IDs
- ACT-385781A
- U-53,217
- U-53217
Pharmacology
- Indication
For the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Pulmonary arterial hypertension ••• ••••• Treatment of Pulmonary arterial hypertension •••••••••••• - Contraindications & Blackbox Warnings
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Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol.
- Mechanism of action
Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacycline (PGI2) from endothelial cells activate G protein-coupled receptors on platelets and endothelial cells. This activation causes adenylate cyclase to produce cyclic AMP which inhibits further platelet activation and activates protein kinase A. Cyclic AMP also prevents coagulation by preventing an increase in intracellular calcium from thromboxane A2 binding. PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists.
Target Actions Organism AProstacyclin synthase inducerHumans AP2Y purinoceptor 12 agonistHumans AProstacyclin receptor agonistHumans - Absorption
Not Available
- Volume of distribution
- 357 mL/kg
- Protein binding
Not Available
- Metabolism
Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
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- Route of elimination
Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
- Half-life
The in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; the in vivo half-life of epoprostenol in humans is therefore expected to be no greater than 6 minutes.
- Clearance
Not Available
- Adverse Effects
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Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of epoprostenol. Single intravenous doses at 10 and 50 mg/kg (2703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Epoprostenol which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Epoprostenol is combined with Abaloparatide. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Epoprostenol. Abrocitinib The risk or severity of bleeding and thrombocytopenia can be increased when Epoprostenol is combined with Abrocitinib. Acebutolol Epoprostenol may increase the hypotensive activities of Acebutolol. - Food Interactions
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Epoprostenol sodium 4K04IQ1OF4 61849-14-7 LMHIPJMTZHDKEW-XQYLJSSYSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Caripul Powder, for solution 0.5 mg / vial Intravenous Janssen Pharmaceuticals 2013-04-24 Not applicable Canada 
Caripul Powder, for solution 1.5 mg / vial Intravenous Janssen Pharmaceuticals 2013-04-24 Not applicable Canada Epoprostenol Injection, powder, lyophilized, for solution 0.5 mg/10mL Intravenous Sun Pharmaceutical Industries, Inc. 2020-11-01 Not applicable US 
Epoprostenol Powder, for solution 1.5 mg/5mL Intravenous GeneraMedix Inc 2008-06-27 2009-03-19 US Epoprostenol Injection, powder, lyophilized, for solution 1.5 mg/10mL Intravenous Sun Pharmaceutical Industries, Inc. 2020-11-01 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Epoprostenol Injection, powder, lyophilized, for solution 1.5 mg/10mL Intravenous Sun Pharmaceutical Industries, Inc. 2021-01-16 Not applicable US Epoprostenol Injection, powder, lyophilized, for solution 0.5 mg/10mL Intravenous Sun Pharmaceutical Industries, Inc. 2021-01-16 Not applicable US Epoprostenol Sodium Injection, powder, for solution 1.5 mg/1 Intravenous Teva Parenteral Medicines, Inc. 2008-04-23 Not applicable US Epoprostenol Sodium Injection, powder, for solution 0.5 mg/1 Intravenous Teva Parenteral Medicines, Inc. 2008-04-23 Not applicable US
Categories
- ATC Codes
- B01AC09 — Epoprostenol
- Drug Categories
- Anticoagulants
- Antihypertensive Agents
- Antiplatelet agents
- Autacoids
- Biological Factors
- Blood and Blood Forming Organs
- Cardiovascular Agents
- Drugs that are Mainly Renally Excreted
- Eicosanoids
- Fatty Acids
- Fatty Acids, Unsaturated
- Hematologic Agents
- Hypotensive Agents
- Inflammation Mediators
- Lipids
- Platelet Aggregation Inhibitors Excl. Heparin
- Prostacyclin Analogues
- Prostacycline Vasodilator
- Prostaglandins
- Prostaglandins I
- Vasodilating Agents
- Vasodilation
- Classification
- Not classified
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- DCR9Z582X0
- CAS number
- 35121-78-9
- InChI Key
- KAQKFAOMNZTLHT-OZUDYXHBSA-N
- InChI
- InChI=1S/C20H32O5/c1-2-3-4-7-14(21)10-11-16-17-12-15(8-5-6-9-20(23)24)25-19(17)13-18(16)22/h8,10-11,14,16-19,21-22H,2-7,9,12-13H2,1H3,(H,23,24)/b11-10+,15-8-/t14-,16+,17+,18+,19-/m0/s1
- IUPAC Name
- 5-[(2Z,3aR,4R,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid
- SMILES
- [H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)CCCCC)[C@@]1([H])C\C(O2)=C\CCCC(O)=O
References
- Synthesis Reference
Nagesh R. Palepu, "NOVEL EPOPROSTENOL FORMULATION AND METHOD OF MAKING THEREOF." U.S. Patent US20090088468, issued April 02, 2009.
US20090088468- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0001335
- KEGG Drug
- D00106
- KEGG Compound
- C01312
- PubChem Compound
- 5280427
- PubChem Substance
- 46507362
- ChemSpider
- 4445566
- 8814
- ChEBI
- 15552
- ChEMBL
- CHEMBL1139
- ZINC
- ZINC000003813078
- Therapeutic Targets Database
- DAP001213
- PharmGKB
- PA449479
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Prostacyclin
- FDA label
- Download (1.28 MB)
- MSDS
- Download (40.6 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Treatment Acute Pulmonary Embolism (PE) 1 4 Completed Treatment Acute Renal Failure (ARF) 1 4 Completed Treatment Cardiovascular Disease (CVD) 1 4 Completed Treatment Heart Failure 1 4 Completed Treatment Oxygenation During One Lung Ventilation 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- GlaxoSmithKline Inc.
- Hollister-Stier Laboratories LLC
- Myogen Inc.
- Sicor Pharmaceuticals
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Powder, for solution Parenteral 0.5 MG Powder, for solution Parenteral 1.5 MG Injection, powder, for solution Parenteral Powder, for solution Intravenous 1.5 mg/5mL Injection, powder, for solution Intravenous 0.5 mg/1 Injection, powder, for solution Intravenous 1.5 mg/1 Powder, for solution Injection, powder, lyophilized, for solution Intravenous 0.5 mg/1 Injection, powder, lyophilized, for solution Intravenous 1.5 mg/1 Powder, for solution Intravenous 0.5 mg / vial Powder, for solution Intravenous 1.5 mg / vial Powder, for solution Parenteral 0.5 MG/50ML Powder, for solution Parenteral 1.5 MG/50ML Injection, powder, for solution Parenteral 0.5 mg Injection, powder, for solution Parenteral 1.5 mg Injection, powder, for solution Intravascular 0.5 mg Injection, powder, lyophilized, for solution Intravenous 0.5 mg/10mL Injection, powder, lyophilized, for solution Intravenous 1.5 mg/10mL Injection, powder, lyophilized, for solution Intravenous 1500000 ng/10mL Injection, powder, for solution 0.5 mg Injection, powder, for solution 1.5 mg Injection, powder, for solution Intravenous 0.5 mg Injection, powder, for solution Intravenous 1.5 mg Injection, powder, lyophilized, for solution Intravenous 0.5 mg - Prices
Unit description Cost Unit Flolan 1.5 mg vial 51.59USD vial Epoprostenol sodium 1.5 mg vial 33.53USD vial Flolan 0.5 mg vial 21.36USD vial Epoprostenol sodium 0.5 mg vial 13.88USD vial DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8598227 No 2013-12-03 2027-02-02 US US8318802 No 2012-11-27 2027-03-15 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source logP 3 Not Available - Predicted Properties
Property Value Source Water Solubility 0.136 mg/mL ALOGPS logP 3.83 ALOGPS logP 2.42 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 4.43 Chemaxon pKa (Strongest Basic) -1.6 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 86.99 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 99.01 m3·mol-1 Chemaxon Polarizability 41.09 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9922 Blood Brain Barrier + 0.8767 Caco-2 permeable + 0.5636 P-glycoprotein substrate Substrate 0.6946 P-glycoprotein inhibitor I Non-inhibitor 0.9131 P-glycoprotein inhibitor II Non-inhibitor 0.8879 Renal organic cation transporter Non-inhibitor 0.8878 CYP450 2C9 substrate Non-substrate 0.8171 CYP450 2D6 substrate Non-substrate 0.8622 CYP450 3A4 substrate Substrate 0.5384 CYP450 1A2 substrate Non-inhibitor 0.5729 CYP450 2C9 inhibitor Non-inhibitor 0.9251 CYP450 2D6 inhibitor Non-inhibitor 0.9401 CYP450 2C19 inhibitor Non-inhibitor 0.75 CYP450 3A4 inhibitor Non-inhibitor 0.6126 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8673 Ames test Non AMES toxic 0.7865 Carcinogenicity Non-carcinogens 0.9555 Biodegradation Not ready biodegradable 0.5964 Rat acute toxicity 2.6928 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8304 hERG inhibition (predictor II) Non-inhibitor 0.8759
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0159-5693000000-d4cdd32893c86bb9479a Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014r-0009000000-66915dd0b546346271ea Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0udi-0009000000-bbcd85ca2cff34879a33 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-1689000000-4bf1a5bc4aa69a63bab7 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0uyi-0039000000-524ca843da5b1724b3ea Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0603-3910000000-6e84faac086df355c14c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01e9-0395000000-0c3529a5cb4801ec19c7 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 216.6150855 predictedDarkChem Lite v0.1.0 [M-H]- 191.8066822 predictedDarkChem Standard v0.1.0 [M-H]- 200.93254 predictedDeepCCS 1.0 (2019) [M+H]+ 217.0788855 predictedDarkChem Lite v0.1.0 [M+H]+ 217.7110855 predictedDarkChem Lite v0.1.0 [M+H]+ 203.3281 predictedDeepCCS 1.0 (2019) [M+Na]+ 216.7125855 predictedDarkChem Lite v0.1.0 [M+Na]+ 216.1760855 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.24062 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inducer
- General Function
- Prostaglandin-i synthase activity
- Specific Function
- Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2).
- Gene Name
- PTGIS
- Uniprot ID
- Q16647
- Uniprot Name
- Prostacyclin synthase
- Molecular Weight
- 57103.385 Da
References
- Nakayama T: Genetic polymorphisms of prostacyclin synthase gene and cardiovascular disease. Int Angiol. 2010 Apr;29(2 Suppl):33-42. [Article]
- Ruan KH, Wu J, Cervantes V: Characterization of the substrate mimic bound to engineered prostacyclin synthase in solution using high-resolution NMR spectroscopy and mutagenesis: implication of the molecular mechanism in biosynthesis of prostacyclin. Biochemistry. 2008 Jan 15;47(2):680-8. Epub 2007 Dec 15. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Guanyl-nucleotide exchange factor activity
- Specific Function
- Receptor for ADP and ATP coupled to G-proteins that inhibit the adenylyl cyclase second messenger system. Not activated by UDP and UTP. Required for normal platelet aggregation and blood coagulation.
- Gene Name
- P2RY12
- Uniprot ID
- Q9H244
- Uniprot Name
- P2Y purinoceptor 12
- Molecular Weight
- 39438.355 Da
References
- Cattaneo M, Lecchi A: Inhibition of the platelet P2Y12 receptor for adenosine diphosphate potentiates the antiplatelet effect of prostacyclin. J Thromb Haemost. 2007 Mar;5(3):577-82. Epub 2006 Dec 7. [Article]
- Yang J, Wu J, Jiang H, Mortensen R, Austin S, Manning DR, Woulfe D, Brass LF: Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem. 2002 Nov 29;277(48):46035-42. Epub 2002 Sep 23. [Article]
- Kobsar AL, Koessler J, Rajkovic MS, Brunner KP, Steigerwald U, Walter U: Prostacyclin receptor stimulation facilitates detection of human platelet P2Y(12) receptor inhibition by the PFA-100 system. Platelets. 2010;21(2):112-6. doi: 10.3109/09537100903440937. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Guanyl-nucleotide exchange factor activity
- Specific Function
- Receptor for prostacyclin (prostaglandin I2 or PGI2). The activity of this receptor is mediated by G(s) proteins which activate adenylate cyclase.
- Gene Name
- PTGIR
- Uniprot ID
- P43119
- Uniprot Name
- Prostacyclin receptor
- Molecular Weight
- 40955.485 Da
References
- Kasza Z, Fetalvero KM, Ding M, Wagner RJ, Acs K, Guzman AK, Douville KL, Powell RJ, Hwa J, Martin KA: Novel signaling pathways promote a paracrine wave of prostacyclin-induced vascular smooth muscle differentiation. J Mol Cell Cardiol. 2009 May;46(5):682-94. doi: 10.1016/j.yjmcc.2009.01.006. Epub 2009 Jan 23. [Article]
- Yang J, Wu J, Jiang H, Mortensen R, Austin S, Manning DR, Woulfe D, Brass LF: Signaling through Gi family members in platelets. Redundancy and specificity in the regulation of adenylyl cyclase and other effectors. J Biol Chem. 2002 Nov 29;277(48):46035-42. Epub 2002 Sep 23. [Article]
- Ibrahim S, Tetruashvily M, Frey AJ, Wilson SJ, Stitham J, Hwa J, Smyth EM: Dominant negative actions of human prostacyclin receptor variant through dimerization: implications for cardiovascular disease. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1802-9. doi: 10.1161/ATVBAHA.110.208900. Epub 2010 Jun 3. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55