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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H32O5
Molecular Weight 352.4651
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of EPOPROSTENOL

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

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

Molecular Formula C20H32O5
Molecular Weight 352.4651
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 2
Optical Activity UNSPECIFIED

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
Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and prostaglandin E2 in anaesthetized dogs.
1980 Mar
Preliminary investigation on the central action of prostacyclin (PGI2) in rats.
1981
Effects of prostacyclin on cardiovascular reflexes from the ventricular epicardium of the dog: comparison with the effects of prostaglandin E2.
1981 Jun
Studies on the behavioral and hypotensive effects of intraventricular prostacyclin (PGI2) in rats.
1981 Nov
Side effects occurring during administration of epoprostenol (prostacyclin, PGI2), in man.
1982 Aug
Effect of prostaglandins on morphine-induced catalepsy in mice.
1983 Sep-Dec
Hypotension induced by prostacyclin treatment during cardiopulmonary bypass does not increase the risk of cerebral complications.
1984 Nov
Proarrhythmic and antiarrhythmic effects of intravenous prostacyclin in man.
1985 Jul
Myocardial ischemia induced by prostacyclin and iloprost.
1985 Jul
Stimulation of prostacyclin production in isolated rat adipocytes by angiotensin II, vasopressin, and bradykinin: evidence for two separate mechanisms of prostaglandin synthesis.
1985 Jun
Depression and prostacyclin infusion.
1986 Aug 30
Prostaglandin I2 and the nitric oxide donor molsidomine have synergistic effects on thromboresistance in man.
1992 Mar
[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
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
Trophic effects of the cyclooxygenase-2 product prostaglandin E(2) in cardiac myocytes.
2002 Feb
Soluble CD40 ligand in pulmonary arterial hypertension: possible pathogenic role of the interaction between platelets and endothelial cells.
2004 Aug 24
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats.
2009 Nov
Effects of PCB126 and 17β-oestradiol on endothelium-derived vasoactive factors in human endothelial cells.
2011 Jul 11
A cardiac-specific robotized cellular assay identified families of human ligands as inducers of PGC-1α expression and mitochondrial biogenesis.
2012
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:05:27 UTC 2023
Edited
by admin
on Sat Dec 16 16:05:27 UTC 2023
Record UNII
DCR9Z582X0
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
EPOPROSTENOL
INN   MART.   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
Epoprostenol [WHO-DD]
Common 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
(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 Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
FDA ORPHAN DRUG 8785
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
LIVERTOX 359
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
NDF-RT N0000011280
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
FDA ORPHAN DRUG 2884
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
FDA ORPHAN DRUG 783
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
NDF-RT N0000011280
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
NCI_THESAURUS C78568
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
FDA ORPHAN DRUG 705119
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
WHO-ATC B01AC09
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
FDA ORPHAN DRUG 121698
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
WHO-VATC QB01AC09
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
NDF-RT N0000009909
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
NCI_THESAURUS C270
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
NDF-RT N0000011280
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
Code System Code Type Description
EVMPD
SUB06581MIG
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
CAS
35121-78-9
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
EPA CompTox
DTXSID5022988
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
NCI_THESAURUS
C61748
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
FDA UNII
DCR9Z582X0
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
RXCUI
8814
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY RxNorm
WIKIPEDIA
PROSTACYCLIN
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
DAILYMED
DCR9Z582X0
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
MERCK INDEX
m9256
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY Merck Index
PUBCHEM
5282411
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
MESH
D011464
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
INN
4725
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
DRUG CENTRAL
1034
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
IUPHAR
1915
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
ChEMBL
CHEMBL1139
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
CHEBI
15552
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
SMS_ID
100000084532
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
DRUG BANK
DB01240
Created by admin on Sat Dec 16 16:05:27 UTC 2023 , Edited by admin on Sat Dec 16 16:05:27 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
MAJOR
METABOLITE LESS ACTIVE -> PARENT
Formed by spontaneous degradation; Pharmacological activity orders of magnitude less than epoprostenol in animal test systems
MAJOR
Related Record Type Details
ACTIVE MOIETY