U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H32O5
Molecular Weight 352.4658
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of EPOPROSTENOL

SMILES

CCCCC[C@@]([H])(/C(/[H])=C(\[H])/[C@]1([H])[C@@]2([H])C/C(=C(\[H])/CCCC(=O)O)/O[C@@]2([H])C[C@@]1([H])O)O

InChI

InChIKey=KAQKFAOMNZTLHT-OZUDYXHBSA-N
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

HIDE SMILES / InChI
Epoprostenol (marketed as FLOLAN, VELETRI) is a prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. Epoprostenol (PGI2, PGX, prostacyclin), a metabolite of arachidonic acid, is a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. FLOLAN (epoprostenol sodium) for Injection is a sterile sodium salt formulated for intravenous (IV) administration. 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. FLOLAN is indicated 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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FLOLAN

Approved Use

FLOLAN is indicated 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.

Launch Date

8.1155523E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
347 pg/mL
2 ng/kg/min other, intravenous
dose: 2 ng/kg/min
route of administration: Intravenous
experiment type: OTHER
co-administered:
6-KETO-PROSTAGLANDIN F1ALPHA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1972 pg × h/mL
2 ng/kg/min other, intravenous
dose: 2 ng/kg/min
route of administration: Intravenous
experiment type: OTHER
co-administered:
6-KETO-PROSTAGLANDIN F1ALPHA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.22 h
2 ng/kg/min other, intravenous
dose: 2 ng/kg/min
route of administration: Intravenous
experiment type: OTHER
co-administered:
6-KETO-PROSTAGLANDIN F1ALPHA plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
8 ng/kg/min single, intravenous
Highest studied dose
Dose: 8 ng/kg/min
Route: intravenous
Route: single
Dose: 8 ng/kg/min
Sources:
healthy, 33.7 years (range: 18–45 years)
n = 20
Health Status: healthy
Age Group: 33.7 years (range: 18–45 years)
Sex: M
Population Size: 20
Sources:
Disc. AE: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Nausea (1 patient)
Vomiting (1 patient)
Sources:
110.5 ng/kg/min multiple, intravenous (max)
Highest studied dose
Dose: 110.5 ng/kg/min
Route: intravenous
Route: multiple
Dose: 110.5 ng/kg/min
Sources:
unhealthy, 42 years
n = 1
Health Status: unhealthy
Condition: pulmonary hypertension
Age Group: 42 years
Sex: M
Population Size: 1
Sources:
0.05 ug/kg/min multiple, respiratory (complex)
Dose: 0.05 ug/kg/min
Route: respiratory
Route: multiple
Dose: 0.05 ug/kg/min
Sources:
unhealthy, 56.4 ± 15.3 years
n = 52
Health Status: unhealthy
Condition: refractory hypoxemia
Age Group: 56.4 ± 15.3 years
Sex: M+F
Population Size: 52
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea 1 patient
Disc. AE
8 ng/kg/min single, intravenous
Highest studied dose
Dose: 8 ng/kg/min
Route: intravenous
Route: single
Dose: 8 ng/kg/min
Sources:
healthy, 33.7 years (range: 18–45 years)
n = 20
Health Status: healthy
Age Group: 33.7 years (range: 18–45 years)
Sex: M
Population Size: 20
Sources:
Vomiting 1 patient
Disc. AE
8 ng/kg/min single, intravenous
Highest studied dose
Dose: 8 ng/kg/min
Route: intravenous
Route: single
Dose: 8 ng/kg/min
Sources:
healthy, 33.7 years (range: 18–45 years)
n = 20
Health Status: healthy
Age Group: 33.7 years (range: 18–45 years)
Sex: M
Population Size: 20
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides.
1976 Nov
Effect of prostaglandins on morphine-induced catalepsy in mice.
1983 Sep-Dec
Severe hypotension due to epoprostenol.
1984 Dec 15
Myocardial ischemia induced by prostacyclin and iloprost.
1985 Jul
Acute effects of captopril on the baroreflex of normotensive and spontaneously hypertensive rats.
1986 Jul
Epoprostenol sodium (prostacyclin) infusion in acute myocardial infarction.
1986 Nov
Myocardial ischemia during intravenous prostacyclin administration: hemodynamic findings and precautionary measures.
1987 Feb
Treatment of primary pulmonary hypertension intravenous epoprostenol (prostacyclin).
1987 Mar
Characterization of the arachidonic acid metabolites mediating bradykinin and noradrenaline hyperalgesia.
1988 Aug 23
Reduction by prostacyclin of acetaminophen-induced liver toxicity in the mouse.
1988 Mar-Apr
Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).
1988 Nov
Prostacyclin I2 (PGI2) increases left ventricular ejection fraction (LVEF).
1989 Jun
Chronic nicotine treatment enhances the depressor responses to arachidonic acid in the rat.
1991
Rat renal papillary release of hypotensive substances in vitro.
1991 Aug
[Massive pulmonary embolism disclosing thrombocytopenia induced by low molecular weight heparin. Therapeutic success of prostacyclin].
1991 Dec
Prostaglandin I2 and the nitric oxide donor molsidomine have synergistic effects on thromboresistance in man.
1992 Mar
Primary pulmonary hypertension and fenfluramine use.
1993 Dec
[Cardioprotective effects by ramipril after ischemia and reperfusion in animal experiment studies].
1994
The effects of prostacyclin on gastric intramucosal pH in patients with septic shock.
1995 May
Systemic and pulmonary hypertension after abrupt cessation of prostacyclin: role of thromboxane A2.
1996 Jan
Paradoxical acute brain thromboembolism during prostacyclin (PGI2) acute challenge for primary pulmonary hypertension.
1996 Jan
Site-directed mutagenesis of human prostacyclin synthase: Alteration of Cys441 of the Cys-pocket, and Glu347 and Arg350 of the EXXR motif.
1996 Jul 8
[Aerosolized prostacyclin for preoperative evaluation and post-cardiosurgical treatment of patients with pulmonary hypertension].
1997 Feb
Primary pulmonary hypertension associated with the use of fenfluramine derivatives.
1998 Sep
Twin pregnancy in a woman on long-term epoprostenol therapy for primary pulmonary hypertension. A case report.
2000 Feb
Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.
2000 Mar 21
Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs.
2000 Nov 7
High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy.
2001
Orthotopic liver transplantation in a patient with severe portopulmonary hypertension.
2001 Apr
Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells.
2001 Feb 1
Epoprostenol sodium, a prostaglandin I2, lacks tumor promoting effects in a medium-term liver carcinogenesis bioassay in rats.
2001 Jan 26
Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand binding techniques.
2002 Apr
Prostacyclin production in rat aortic smooth muscle cells: role of protein kinase C, phospholipase D and cyclooxygenase-2 expression.
2003 Nov 1
Cocaine affects prostaglandin production in human umbilical cord cell cultures.
2003 Oct
Soluble CD40 ligand in pulmonary arterial hypertension: possible pathogenic role of the interaction between platelets and endothelial cells.
2004 Aug 24
Prostacyclin inhibition by indomethacin aggravates hepatic damage and encephalopathy in rats with thioacetamide-induced fulminant hepatic failure.
2005 Jan 14
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
COX-2-derived prostacyclin modulates vascular remodeling.
2005 Jun 24
Correlation between right ventricular indices and clinical improvement in epoprostenol treated pulmonary hypertension patients.
2005 May
Imbalanced synthesis of cyclooxygenase-derived thromboxane A2 and prostacyclin compromises vasomotor function of the thoracic aorta in Marfan syndrome.
2007 Oct
Treatment of pulmonary arterial hypertension in pregnancy.
2007 Sep 15
Estrogen protects the heart from ischemia-reperfusion injury via COX-2-derived PGI2.
2008 Sep
Prostacyclin (epoprostenol) induces headache in healthy subjects.
2008 Sep 30
Prothrombotic effects of diclofenac on arteriolar platelet activation and thrombosis in vivo.
2009 Oct
Effects of PCB126 and 17β-oestradiol on endothelium-derived vasoactive factors in human endothelial cells.
2011 Jul 11
Endometrial HSD11B1 and cortisol regeneration in the ovine uterus: effects of pregnancy, interferon tau, and prostaglandins.
2012 Apr
Patents

Sample Use Guides

Usual Adult Dose for Pulmonary Hypertension Acute Dose Ranging: 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited. The mean maximum dose which did not elicit dose-limiting pharmacologic effects was 8.6 ng/kg/min. Continuous Chronic Infusion: 4 ng/kg/min less than the maximum tolerated infusion rate determined during acute dose ranging. If the maximum tolerated infusion rate is less than 5 ng/kg/min, the chronic infusion should be started at one-half the maximum tolerated infusion rate. During clinical trials, the mean initial chronic infusion rate was 5 ng/kg/min.
Route of Administration: Intravenous
Addition of prostacyclin (Epoprostenol) (10(–8)–10(–5) mol/L) to KCl-stimulated human intrarenal arteries yielded concentration-dependent relaxations ≤10(–6) mol/L (EC50: −log 7.7 mol/L). At concentrations of prostacyclin >10(–6) mol/L, the relaxation reversed to a significant increase in tension.
Name Type Language
EPOPROSTENOL
INN   MART.   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
ACT-385781A
Code English
U-53217
Code English
PROSTA-5,13-DIEN-1-OIC ACID, 6,9-EPOXY-11,15-DIHYDROXY-, (5Z,9.ALPHA.,11.ALPHA.,13E,15S)-
Common Name English
U-53,217
Code English
EPOPROSTENOL [WHO-DD]
Common Name English
(Z)-(3AR,4R,5R,6AS)-HEXAHYDRO-5-HYDROXY-4-((E)-(3S)-3-HYDROXY-1-OCTENYL)-2H-CYCLOPENTA(B)FURAN-.DELTA.(SUP 2,.DELTA.)-VALERATE
Common Name English
PROSTACYCLIN [MI]
Common Name English
EPOPROSTENOL [USAN]
Common Name English
EPOPROSTENOL [INN]
Common Name English
PROSTACYCLIN
MI  
Common Name English
EPOPROSTENOL [MART.]
Common Name English
EPOPROSTENOL [VANDF]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175416
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
FDA ORPHAN DRUG 8785
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
LIVERTOX 359
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
NDF-RT N0000011280
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
FDA ORPHAN DRUG 2884
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
FDA ORPHAN DRUG 783
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
NDF-RT N0000011280
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
NCI_THESAURUS C78568
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
FDA ORPHAN DRUG 705119
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
WHO-ATC B01AC09
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
FDA ORPHAN DRUG 121698
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
WHO-VATC QB01AC09
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
NDF-RT N0000009909
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
NCI_THESAURUS C270
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
NDF-RT N0000011280
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
Code System Code Type Description
EVMPD
SUB06581MIG
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
CAS
35121-78-9
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
EPA CompTox
35121-78-9
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
NCI_THESAURUS
C61748
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
FDA UNII
DCR9Z582X0
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
RXCUI
8814
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY RxNorm
WIKIPEDIA
PROSTACYCLIN
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
MERCK INDEX
M9256
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY Merck Index
PUBCHEM
5282411
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
MESH
D011464
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
INN
4725
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
DRUG CENTRAL
1034
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
IUPHAR
1915
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
ChEMBL
CHEMBL1139
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY
DRUG BANK
DB01240
Created by admin on Sat Jun 26 09:55:58 UTC 2021 , Edited by admin on Sat Jun 26 09:55:58 UTC 2021
PRIMARY