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
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
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
1398.0 nM [Ki] | |||
Target ID: Q9H244 Gene ID: 64805.0 Gene Symbol: P2RY12 Target Organism: Homo sapiens (Human) |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | FLOLAN Approved UseFLOLAN 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 Date1995 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
347 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22515646/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1972 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22515646/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.22 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22515646/ |
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
Dose | Population | Adverse 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) Sources: Vomiting (1 patient) |
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
AE | Significance | Dose | Population |
---|---|---|---|
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: |
PubMed
Title | Date | PubMed |
---|---|---|
Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. | 1976 Nov |
|
Inhibition of epinephrine-exacerbated coronary thrombus formation by prostacyclin in the dog. | 1984 Feb |
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Plasma concentrations, renal excretion, and tissue release of prostaglandins in the rat with dexamethasone-induced hypertension. | 1984 Mar |
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Proarrhythmic and antiarrhythmic effects of intravenous prostacyclin in man. | 1985 Jul |
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Stimulation of prostacyclin production in isolated rat adipocytes by angiotensin II, vasopressin, and bradykinin: evidence for two separate mechanisms of prostaglandin synthesis. | 1985 Jun |
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Depression and prostacyclin infusion. | 1986 Aug 30 |
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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 |
|
Treatment of primary pulmonary hypertension intravenous epoprostenol (prostacyclin). | 1987 Mar |
|
Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin). | 1988 Nov |
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Prostacyclin I2 (PGI2) increases left ventricular ejection fraction (LVEF). | 1989 Jun |
|
[Responses of plasma eicosanoids and hemodynamics to myocardial ischemia and the salutary effect of calcium entry blocker]. | 1990 Feb |
|
Chronic nicotine treatment enhances the depressor responses to arachidonic acid in the rat. | 1991 |
|
Further confirmation of the role of adenyl cyclase and of cAMP-dependent protein kinase in primary afferent hyperalgesia. | 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 |
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Prostaglandin I2 and the nitric oxide donor molsidomine have synergistic effects on thromboresistance in man. | 1992 Mar |
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Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery. | 1992 Sep |
|
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 |
|
Primary pulmonary hypertension associated with the use of fenfluramine derivatives. | 1998 Sep |
|
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 |
|
The use of inhaled prostacyclin in nitroprusside-resistant pulmonary artery hypertension. | 2001 Dec |
|
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 |
|
Effects of transmitters and interleukin-10 on rat hepatic fibrosis induced by CCl4. | 2003 Mar |
|
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 |
|
Reversal of pulmonary hypertension and subsequent repair of atrial septal defect after treatment with continuous intravenous epoprostenol. | 2005 Apr |
|
Staggered transition to epoprostenol from treprostinil in pulmonary arterial hypertension. | 2005 Apr |
|
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 |
|
Prostacyclin receptor up-regulates the expression of angiogenic genes in human endometrium via cross talk with epidermal growth factor Receptor and the extracellular signaling receptor kinase 1/2 pathway. | 2006 Apr |
|
Bradykinin B2 receptor knockout mice are protected from thrombosis by increased nitric oxide and prostacyclin. | 2006 Jul 1 |
|
Effects of vascular endothelial growth factor receptor inhibitor SU5416 and prostacyclin on murine lung metastasis. | 2007 Mar |
|
Traditional nonsteroidal anti-inflammatory drugs and postmenopausal hormone therapy: a drug-drug interaction? | 2007 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 |
|
Prostacyclin treatment normalises the MCA flow velocity in nimodipine-resistant cerebral vasospasm after aneurysmal subarachnoid haemorrhage: a pilot study. | 2009 Jun |
|
A cardiac-specific robotized cellular assay identified families of human ligands as inducers of PGC-1α expression and mitochondrial biogenesis. | 2012 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/epoprostenol.html
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24914192
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
Edited
Sat Dec 16 16:05:27 GMT 2023
by
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Record UNII |
DCR9Z582X0
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175416
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FDA ORPHAN DRUG |
8785
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LIVERTOX |
359
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N0000011280
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FDA ORPHAN DRUG |
2884
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FDA ORPHAN DRUG |
783
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N0000011280
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NCI_THESAURUS |
C78568
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FDA ORPHAN DRUG |
705119
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WHO-ATC |
B01AC09
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FDA ORPHAN DRUG |
121698
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WHO-VATC |
QB01AC09
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N0000009909
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NCI_THESAURUS |
C270
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NDF-RT |
N0000011280
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35121-78-9
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8814
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PROSTACYCLIN
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m9256
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5282411
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D011464
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CHEMBL1139
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15552
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100000084532
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DB01240
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SALT/SOLVATE -> PARENT |
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METABOLITE LESS ACTIVE -> PARENT |
MAJOR
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METABOLITE LESS ACTIVE -> PARENT |
Formed by spontaneous degradation; Pharmacological activity orders of magnitude less than epoprostenol in animal test systems
MAJOR
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ACTIVE MOIETY |