Identification
- Summary
Treprostinil is a prostacyclin vasodilator for the treatment of pulmonary arterial hypertension to relieve exercise associated symptoms and to prevent clinical deterioration after stopping epoprostenol.
- Brand Names
- Orenitram, Remodulin, Tyvaso
- Generic Name
- Treprostinil
- DrugBank Accession Number
- DB00374
- Background
Treprostinil is a stable tricyclic analogue of prostacyclin3 that promotes the vasodilation of pulmonary and systemic arterial vascular beds and the inhibition of platelet aggregation.5,6,7 It reduces symptoms in patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease.5,6 The first agent approved for the treatment of PAH was epoprostenol, a synthetic prostacyclin that significantly increases patients' quality of life. However, the use of epoprostenol is limited due to its short half-life (3-5 min) and instability at room temperature.3,4 The use of more stable alternatives such as treprostinil provides patients with PAH with more treatment options.
Treprostinil was approved by the FDA in 2002 for the treatment of pulmonary arterial hypertension.6 It is available in the following routes of administration: subcutaneous, intravenous, inhaled and oral. The first generic form of treprostinil became available in 2019.4
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Treprostinil (DB00374)
- Weight
- Average: 390.5131
Monoisotopic: 390.240624198 - Chemical Formula
- C23H34O5
- Synonyms
- Treprostinil
- Tréprostinil
- Treprostinilo
- Treprostinilum
- External IDs
- 15AU81
- BW 15AU
- LRX 15
- LRX-15
- U 62840
- UT 15
- UT-15
- UT-15C
Pharmacology
- Indication
The FDA has indicated treprostinil for the treatment of pulmonary arterial hypertension5,6,7 and pulmonary hypertension associated with interstitial lung disease5 to improve exercise ability. It is also used to treat pulmonary arterial hypertension in patients requiring transition from epoprostenol.6 The Health Canada label specifies that treprostinil is indicated for the long-term treatment of pulmonary arterial hypertension in NYHA Class III and IV patients who did not respond adequately to conventional therapy.11
L24244
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Pulmonary arterial hypertension (pah) •••••••••••• Management of Pulmonary arterial hypertension (pah) •••••••••••• Treatment of Pulmonary arterial hypertension (pah) •••••••••••• •••••••• Treatment of Pulmonary arterial hypertension (pah) •••••••••••• •••••••• Management of Pulmonary hypertension (ph) •••••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
As an analogue of prostacyclin, treprostinil promotes the vasodilation of pulmonary and systemic arterial vascular beds and the inhibition of platelet aggregation 5,6,7. In animals, the vasodilatory effects of treprostinil lead to a reduction of right and left ventricular afterload and an increase in cardiac output and stroke volume.6 Treprostinil also causes a dose-related negative inotropic and lusitropic effect, and no major effects on cardiac conduction have been detected.6 Short-lasting effects on QTc were detected in healthy volunteers (n=240) given inhaled single doses of 54 and 84 μg of treprostinil. These effects dissipated rapidly as treprostinil concentrations lowered.5 When given subcutaneously or intravenously, treprostinil has the potential to reach higher concentrations.6 The effect of oral treprostinil on QTc has not been evaluated.7
Due to its ability to inhibit platelet aggregation, treprostinil can increase the risk of bleeding, and patients with low systemic arterial pressure taking treprostinil may experience symptomatic hypotension.5,6 The abrupt withdrawal of treprostinil or drastic changes in dose may worsen the symptoms of pulmonary arterial hypertension (PAH).6,7 The inhalation of treprostinil can also cause bronchospasms in patients with asthma, chronic obstructive pulmonary disease (COPD), or bronchial hyperreactivity.5 When given intravenously, treprostinil can lead to infusion complications and increase the risk of bloodstream infections.6
- Mechanism of action
Treprostinil is a stable analogue of prostacyclin5,6,7, a prostaglandin that acts as an anti-thrombotic agent and a potent vasodilator. Prostacyclin analogues are useful in the treatment of pulmonary arterial hypertension (PAH), a disease characterized by abnormally high blood pressure in the arteries between the heart and lungs.3 PAH leads to right heart failure due to the remodelling of pulmonary arteries, and patients with this condition have a poor prognosis.4
Treprostinil binds and activates the prostacyclin receptor, the prostaglandin D2 receptor 1, and the prostaglandin E2 receptor 2.3 The activation of these receptors leads to the elevation of intracellular cyclic adenosine monophosphate (cAMP) levels, which consequently promotes the opening of calcium-activated potassium channels that lead to cell hyperpolarization.3 This mechanism promotes the direct vasodilation of pulmonary and systemic arterial vascular beds and the inhibition of platelet aggregation1,5,6,7. In addition to its direct vasodilatory effects, treprostinil inhibits inflammatory pathways.2
Target Actions Organism AProstacyclin receptor agonistHumans AProstaglandin E2 receptor EP2 subtype agonistHumans AProstaglandin D2 receptor agonistHumans APeroxisome proliferator-activated receptor delta agonistHumans UP2Y purinoceptor 12 agonistHumans - Absorption
After subcutaneous infusion, treprostinil is completely absorbed, with a bioavailability of about 100%, and it reaches steady-state concentrations in approximately 10 hours.6 The pharmacokinetics of treprostinil follow a two-compartment model and are linear between 2.5 and 125 ng/kg/min.6 Subcutaneous and intravenous doses of treprostinil are bioequivalent at 10 ng/kg/min. Compared to healthy subjects, patients with mild and moderate hepatic insufficiency had a corresponding Cmax 2- and 4-times higher and an AUC0-∞ 3- and 5-times higher when given a subcutaneous treprostinil dose of 10 ng/kg/min for 150 min.6
When given orally at doses between 0.5 and 15 mg twice a day, treprostinil follows a dose-proportional pharmacokinetic profile.7 The oral bioavailability of treprostinil is 17%, and drug concentration reaches its highest level between 4 and 6 hours after oral administration.7 The oral absorption of treprostinil is affected by food. The AUC and Cmax of oral treprostinil increase 49% and 13%, respectively, when this drug is administered with a high-fat, high-calorie meal.7
The AUC and Cmax of inhaled treprostinil were proportional to the doses administered (18 to 90 μg).5 The bioavailability of inhaled treprostinil was 64% in patients receiving 2 doses of 18 μg, and 72% in patients receiving two doses of 36 μg.5 Two separate studies that evaluated the pharmacokinetics of inhaled treprostinil at a maintenance dose of 54 μg found that the mean Cmax was 0.91 and 1.32 ng/mL, respectively, with a corresponding Tmax of 0.25 and 0.12 hr and a mean AUC of 0.81 and 0.97 hr⋅ng/mL.5
- Volume of distribution
The volume of distribution of treprostinil is 14 L/70 kg.5,6
- Protein binding
At in vitro concentrations ranging from 330 to 10,000 μg/L, the human plasma protein binding of treprostinil is approximately 91%. This concentration is above what is considered to be clinically relevant.6
- Metabolism
Treprostinil is mostly metabolized by the liver, mainly by CYP2C8, and by CYP2C9 to a lesser extent.5,6,7 Treprostinil does not have a single major metabolite. The five metabolites detected in urine (HU1 through HU5) accounted for 13.8, 14.3, 15.5, 10.6 and 10.2% of the dose, respectively.8 One of the metabolites (HU5) is the glucuronide conjugate of treprostinil. HU1, HU2, HU3 and HU4 are formed through the oxidation of the 3-hydroxyloctyl side chain.5,6,7,8 None of the metabolites of treprostinil appear to be active. In vitro studies suggest that treprostinil does not inhibit or induce any major CYP enzymes.5,6
Hover over products below to view reaction partners
- Route of elimination
Treprostinil metabolites are excreted through urine (79%) and feces (13%) over 10 days.5,6 Only a small proportion of treprostinil is excreted unchanged. When administered orally, 1.13% and 0.19% of unchanged treprostinil diolamine are found in urine and feces, respectively.7 When administered subcutaneously, intravenously or by inhalation, 4% of unchanged treprostinil is found in urine.5,6
- Half-life
The terminal elimination half-life of treprostinil is approximately 4 hours, following a two-compartment model.5,6
- Clearance
The clearance of treprostinil is 30 L/hr in a 70 kg person.6 In patients with mild to moderate hepatic insufficiency, clearance is reduced up to 80%.5
- Adverse Effects
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Treprostinil overdose symptoms are an extension of its dose-limiting pharmacologic effects.6 These include flushing, headache, hypotension, nausea, vomiting, and diarrhea.5,6,7 Most overdose events were self-limiting and resolved by reducing or withholding treprostinil.6 In studies where treprostinil was infused using an external pump, several patients received an overdose due to an accidental bolus administration, errors in the programmed delivery rate and incorrect prescriptions. Only two cases of of substantial hemodynamic concern were detected among patients that received an excess of treprostinil.6 A pediatric patient that accidentally received 7.5 mg of treprostinil via a central venous catheter presented flushing, headache, nausea, vomiting, hypotension, and seizure-like activity with loss of consciousness for several minutes.6
A rat study that evaluated the carcinogenic effects of inhaled treprostinil, found no evidence of carcinogenicity in levels up to 35 times the clinical exposure obtained with a maintenance dose of 54 μg.5 The infusion of treprostinil sodium did not affect fertility or mating performance in rats given subcutaneous treprostinil.6 Treprostinil did not show mutagenic or clastogenic effects in in vitro or in vivo studies.5,6 There was no significant increase of tumors in rats given up to 10 mg/kg/day of oral treprostinil diolamine.7
- 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 softwareAbaloparatide Abaloparatide may increase the hypotensive activities of Treprostinil. Abatacept The metabolism of Treprostinil can be increased when combined with Abatacept. Abciximab Treprostinil may increase the antiplatelet activities of Abciximab. Abiraterone The metabolism of Treprostinil can be decreased when combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Treprostinil. - Food Interactions
- Take with food. Taking treprostinil with food increases oral absorption.
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 Treprostinil diolamine H1FKG90039 830354-48-8 RHWRWEUCEXUUAV-ZSESPEEFSA-N Treprostinil sodium 7JZ75N2NT6 289480-64-4 IQKAWAUTOKVMLE-ZSESPEEFSA-M - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Orenitram Tablet, extended release 5 mg/1 Oral United Therapeutics Corporation 2013-12-20 Not applicable US 
Orenitram Tablet, extended release 0.25 mg/1 Oral United Therapeutics Corporation 2013-12-20 Not applicable US Orenitram Tablet, extended release 0.125 mg/1 Oral United Therapeutics Corporation 2013-12-20 Not applicable US Orenitram Tablet, extended release 2.5 mg/1 Oral United Therapeutics Corporation 2013-12-20 Not applicable US Orenitram Tablet, extended release 2.5 mg/1 Oral Avera McKennan Hospital 2016-07-20 2017-05-24 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Treprostinil Injection, solution 50 mg/20mL Intravenous; Subcutaneous Dr.Reddy's Laboratories Inc., 2023-02-13 Not applicable US Treprostinil Injection, solution 20 mg/20mL Intravenous; Subcutaneous Alembic Pharmaceuticals Inc. 2021-02-11 Not applicable US Treprostinil Injection 50 mg/20mL Intravenous; Subcutaneous Sandoz Inc 2019-03-25 Not applicable US Treprostinil Injection, solution 1 mg/1mL Intravenous; Subcutaneous Par Pharmaceutical, Inc. 2019-09-25 Not applicable US Treprostinil Injection, solution 100 mg/20mL Intravenous; Subcutaneous Teva Parenteral Medicines, Inc. 2019-09-30 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Orenitram Treprostinil (0.125 mg/1) + Treprostinil (0.25 mg/1) Kit; Tablet, extended release Oral United Therapeutics Corporation 2023-02-14 Not applicable US Orenitram Treprostinil (0.125 mg/1) + Treprostinil (0.25 mg/1) Kit; Tablet, extended release Oral United Therapeutics Corporation 2023-02-14 Not applicable US Orenitram Treprostinil (0.125 mg/1) + Treprostinil (0.25 mg/1) + Treprostinil (1 mg/1) Kit; Tablet, extended release Oral United Therapeutics Corporation 2023-02-14 Not applicable US Orenitram Treprostinil (0.125 mg/1) + Treprostinil (0.25 mg/1) Kit; Tablet, extended release Oral United Therapeutics Corporation 2023-02-14 Not applicable US Orenitram Treprostinil (0.125 mg/1) + Treprostinil (0.25 mg/1) + Treprostinil (1 mg/1) Kit; Tablet, extended release Oral United Therapeutics Corporation 2023-02-14 Not applicable US
Categories
- ATC Codes
- B01AC21 — Treprostinil
- Drug Categories
- Antihypertensive Agents
- Autacoids
- Biological Factors
- Blood and Blood Forming Organs
- Cardiovascular Agents
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 Substrates
- Eicosanoids
- Fatty Acids
- Fatty Acids, Unsaturated
- Inflammation Mediators
- Lipids
- Platelet Aggregation Inhibitors Excl. Heparin
- Potential QTc-Prolonging Agents
- Prostacyclin Analogues
- Prostacycline Vasodilator
- Prostaglandins
- Prostaglandins I
- QTc Prolonging Agents
- Vasodilating Agents
- Vasodilation
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenoxyacetic acid derivatives. These are compounds containing an anisole where the methane group is linked to an acetic acid or a derivative.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Phenoxyacetic acid derivatives
- Direct Parent
- Phenoxyacetic acid derivatives
- Alternative Parents
- Tetralins / Fatty alcohols / Alkyl aryl ethers / Secondary alcohols / Cyclic alcohols and derivatives / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
- Substituents
- Alcohol / Alkyl aryl ether / Aromatic homopolycyclic compound / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclic alcohol / Ether / Fatty acyl / Fatty alcohol
- Molecular Framework
- Aromatic homopolycyclic compounds
- External Descriptors
- carboxylic acid, carbotricyclic compound (CHEBI:50861)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- RUM6K67ESG
- CAS number
- 81846-19-7
- InChI Key
- PAJMKGZZBBTTOY-ZFORQUDYSA-N
- InChI
- InChI=1S/C23H34O5/c1-2-3-4-7-17(24)9-10-18-19-11-15-6-5-8-22(28-14-23(26)27)20(15)12-16(19)13-21(18)25/h5-6,8,16-19,21,24-25H,2-4,7,9-14H2,1H3,(H,26,27)/t16-,17-,18+,19-,21+/m0/s1
- IUPAC Name
- 2-{[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-1H,2H,3H,3aH,4H,9H,9aH-cyclopenta[b]naphthalen-5-yl]oxy}acetic acid
- SMILES
- [H][C@]12C[C@@H](O)[C@H](CC[C@@H](O)CCCCC)[C@@]1([H])CC1=C(C2)C(OCC(O)=O)=CC=C1
References
- Synthesis Reference
Hitesh, B., et al. (2015). Treprostinil production (U.S. Patent No. 8,940,930 B2) U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/1d/63/6e/c2a1143b85274e/US8940930.pdf
US20110319641- General References
- Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P: The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med. 2017 Jun;11(6):491-503. doi: 10.1080/17476348.2017.1317599. Epub 2017 Apr 24. [Article]
- Ding M, Tolbert E, Birkenbach M, Akhlaghi F, Gohh R, Ghonem NS: Treprostinil, a prostacyclin analog, ameliorates renal ischemia-reperfusion injury: preclinical studies in a rat model of acute kidney injury. Nephrol Dial Transplant. 2021 Jan 25;36(2):257-266. doi: 10.1093/ndt/gfaa236. [Article]
- Lindegaard Pedersen M, Kruger M, Grimm D, Infanger M, Wehland M: The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. Basic Clin Pharmacol Toxicol. 2019 Aug 12. doi: 10.1111/bcpt.13305. [Article]
- Feldman J, Habib N, Fann J, Radosevich JJ: Treprostinil in the treatment of pulmonary arterial hypertension. Future Cardiol. 2020 Nov;16(6):547-558. doi: 10.2217/fca-2020-0021. Epub 2020 May 11. [Article]
- FDA Approved Drug Products: TYVASO (treprostinil) inhalation solution, for oral inhalation use [Link]
- FDA Approved Drug Products: REMODULIN (treprostinil) injection, for subcutaneous or intravenous use [Link]
- FDA Approved Drug Products: ORENITRAM (treprostinil) extended-release tablets, for oral use [Link]
- FDA Pharmacology Review: REMODULIN (treprostinil) injection, for subcutaneous or intravenous use [Link]
- Par Pharmaceutical: Treprostinil SDS [Link]
- FDA Clinical Pharmacology and Biopharmaceutics Review: ORENITRAM (treprostinil) extended-release tablets, for oral use [Link]
- Product monograph: Remodulin (Treprostinil) Solution [Link]
- External Links
- Human Metabolome Database
- HMDB0014518
- PubChem Compound
- 6918140
- PubChem Substance
- 46504572
- ChemSpider
- 5293353
- 343048
- ChEBI
- 50861
- ChEMBL
- CHEMBL1237119
- ZINC
- ZINC000003800475
- Therapeutic Targets Database
- DAP001214
- PharmGKB
- PA164768801
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Treprostinil
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 Pulmonary Arterial Hypertension (PAH) 5 4 Completed Treatment Pulmonary Arterial Hypertension (PAH) / Pulmonary Hypertension (PH) 1 4 Completed Treatment Pulmonary Hypertension (PH) 2 4 Recruiting Other Pulmonary Hypertension (PH) 1 4 Recruiting Treatment Pulmonary Arterial Hypertension (PAH) 1
Pharmacoeconomics
- Manufacturers
- United therapeutics corp
- Packagers
- Baxter International Inc.
- United Therapeutics Corp.
- Dosage Forms
Form Route Strength Kit; tablet, extended release Oral Tablet, extended release Oral 0.125 mg/1 Tablet, extended release Oral 0.25 mg/1 Tablet, extended release Oral 1 mg/1 Tablet, extended release Oral 2.5 mg/1 Tablet, extended release Oral 5 mg/1 Injection, solution Intravenous; Subcutaneous 100 mg/20mL Injection, solution Intravenous; Subcutaneous 2 mg/20mL Injection, solution Intravenous; Subcutaneous 20 mg/20mL Injection, solution Intravenous; Subcutaneous 200 mg/20mL Injection, solution Intravenous; Subcutaneous 4 mg/20mL Injection, solution Intravenous; Subcutaneous 400 mg/20mL Injection, solution Intravenous; Subcutaneous 50 mg/20mL Injection, solution Intravenous; Subcutaneous 8 mg/20mL Injection, solution Parenteral 5 MG/ML Solution Intravenous; Subcutaneous 1 mg / mL Solution Intravenous; Subcutaneous 10 mg / mL Solution Intravenous; Subcutaneous 2.5 mg / mL Solution Intravenous; Subcutaneous 5 mg / mL Solution Intravenous; Subcutaneous 1 mg Solution Intravenous; Subcutaneous 10 mg Solution Intravenous; Subcutaneous 5 mg Solution Parenteral Solution Intravenous; Subcutaneous 2.5 mg Injection Parenteral 100 mg/20ml Injection Parenteral 50 mg/20ml Solution Parenteral 1 mg/ml Solution Parenteral 10 mg/ml Solution Parenteral 2.5 mg/ml Solution Parenteral 5 mg/ml Injection Intravenous; Subcutaneous 100 mg/20mL Injection Intravenous; Subcutaneous 20 mg/20mL Injection Intravenous; Subcutaneous 200 mg/20mL Injection Intravenous; Subcutaneous 50 mg/20mL Injection, solution Intravenous; Subcutaneous 1 mg/1mL Injection, solution Intravenous; Subcutaneous 10 mg/1mL Injection, solution Intravenous; Subcutaneous 2.5 mg/1mL Injection, solution Intravenous; Subcutaneous 5 mg/1mL Injection, solution Parenteral 1 MG/ML Injection, solution Parenteral 10 MG/ML Injection, solution Parenteral 2.5 MG/ML Injection, solution 1 MG/ML Injection, solution 10 MG/ML Injection, solution 2.5 MG/ML Injection, solution 5 MG/ML Injection, solution Subcutaneous 1 MG/ML Injection, solution Subcutaneous 10 MG/ML Injection, solution Subcutaneous 2.5 MG/ML Injection, solution Subcutaneous 5 MG/ML Inhalant Oral 1.74 mg/2.9mL Inhalant Oral 16 ug/1 Inhalant Oral 32 ug/1 Inhalant Oral 48 ug/1 Inhalant Oral 64 ug/1 Inhalant; kit Oral Solution Respiratory (inhalation) 0.6 mg - Prices
Unit description Cost Unit Remodulin 10 mg/ml vial 737.0USD ml Remodulin 5 mg/ml vial 368.5USD ml Tyvaso inhalation starter kit 185.8USD ml Remodulin 2.5 mg/ml vial 184.25USD ml Tyvaso 1.74 mg/2.9 ml solution 174.55USD ml Tyvaso inhalation refill kit 165.68USD ml Remodulin 1 mg/ml vial 73.7USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5153222 No 1992-10-06 2014-10-06 US US8653137 No 2014-02-18 2028-09-05 US US8658694 No 2014-02-25 2028-09-05 US US7999007 No 2011-08-16 2029-03-29 US US9199908 No 2015-12-01 2024-05-24 US US6765117 No 2004-07-20 2017-10-24 US US8497393 No 2013-07-30 2028-12-15 US US6521212 No 2003-02-18 2018-11-13 US US6756033 No 2004-06-29 2018-11-13 US US7544713 No 2009-06-09 2024-07-14 US US9278901 No 2016-03-08 2024-05-24 US US7417070 No 2008-08-26 2026-07-30 US US8410169 No 2013-04-02 2030-02-13 US US9050311 No 2015-06-09 2024-05-24 US US8252839 No 2012-08-28 2024-05-24 US US8747897 No 2014-06-10 2029-10-08 US US8349892 No 2013-01-08 2031-01-22 US US9593066 No 2017-03-14 2028-12-15 US US9604901 No 2017-03-28 2028-12-15 US US9339507 No 2016-05-17 2028-03-10 US US9358240 No 2016-06-07 2028-05-05 US US9422223 No 2016-08-23 2024-05-24 US US9393203 No 2016-07-19 2026-04-27 US US9713599 No 2017-07-25 2024-12-16 US US10076505 No 2018-09-18 2024-12-16 US US10376525 No 2019-08-13 2027-05-14 US US10716793 No 2020-07-21 2027-05-14 US US10695308 No 2020-06-30 2024-12-16 US US10772883 No 2020-09-15 2030-06-11 US US10130685 No 2018-11-20 2025-08-23 US US10421729 No 2019-09-24 2035-04-01 US US11723887 No 2008-12-15 2028-12-15 US US11826327 No 2022-01-04 2042-01-04 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 90-100°C SDS water solubility 800 mg/mL FDA Clinical Pharmacology and Biopharmaceutics Review: ORENITRAM (treprostinil) extended-release tablets, for oral use logP 3 FDA Clinical Pharmacology and Biopharmaceutics Review: ORENITRAM (treprostinil) extended-release tablets, for oral use - Predicted Properties
Property Value Source Water Solubility 0.00731 mg/mL ALOGPS logP 3.53 ALOGPS logP 4 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 3.76 Chemaxon pKa (Strongest Basic) -1.3 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 108 m3·mol-1 Chemaxon Polarizability 45.75 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.994 Blood Brain Barrier + 0.5541 Caco-2 permeable + 0.5838 P-glycoprotein substrate Substrate 0.7733 P-glycoprotein inhibitor I Non-inhibitor 0.719 P-glycoprotein inhibitor II Non-inhibitor 0.7518 Renal organic cation transporter Non-inhibitor 0.8064 CYP450 2C9 substrate Non-substrate 0.7811 CYP450 2D6 substrate Non-substrate 0.8144 CYP450 3A4 substrate Substrate 0.6538 CYP450 1A2 substrate Inhibitor 0.7312 CYP450 2C9 inhibitor Non-inhibitor 0.8496 CYP450 2D6 inhibitor Non-inhibitor 0.9127 CYP450 2C19 inhibitor Non-inhibitor 0.6214 CYP450 3A4 inhibitor Non-inhibitor 0.6587 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6885 Ames test Non AMES toxic 0.8716 Carcinogenicity Non-carcinogens 0.9452 Biodegradation Not ready biodegradable 0.7495 Rat acute toxicity 2.0749 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9588 hERG inhibition (predictor II) Inhibitor 0.7664
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-0fxw-4197000000-f2c1b87e66efdc91b50e Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0ab9-0009000000-1e792160c833cd8d664c Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-1009000000-97bf33c02aac0106fac0 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0a4i-2129000000-2d79cad543ec9d5d5026 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01p9-1049000000-bedd44fdf4f1cc09292a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052f-9401000000-d64e68cde8f986d8a51f Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-020d-2192000000-3f3440618fa534272886 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]- 212.6440226 predictedDarkChem Lite v0.1.0 [M-H]- 197.27916 predictedDeepCCS 1.0 (2019) [M+H]+ 209.6915226 predictedDarkChem Lite v0.1.0 [M+H]+ 199.67471 predictedDeepCCS 1.0 (2019) [M+Na]+ 210.8858226 predictedDarkChem Lite v0.1.0 [M+Na]+ 205.64925 predictedDeepCCS 1.0 (2019)
Targets
- 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
- Falcetti E, Hall SM, Phillips PG, Patel J, Morrell NW, Haworth SG, Clapp LH: Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010 Nov 1;182(9):1161-70. doi: 10.1164/rccm.201001-0011OC. Epub 2010 Jul 9. [Article]
- Sprague RS, Bowles EA, Hanson MS, DuFaux EA, Sridharan M, Adderley S, Ellsworth ML, Stephenson AH: Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes. Microcirculation. 2008 Jul;15(5):461-71. doi: 10.1080/10739680701833804. [Article]
- Olschewski H, Rose F, Schermuly R, Ghofrani HA, Enke B, Olschewski A, Seeger W: Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacol Ther. 2004 May;102(2):139-53. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Lindegaard Pedersen M, Kruger M, Grimm D, Infanger M, Wehland M: The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. Basic Clin Pharmacol Toxicol. 2019 Aug 12. doi: 10.1111/bcpt.13305. [Article]
- Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P: The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med. 2017 Jun;11(6):491-503. doi: 10.1080/17476348.2017.1317599. Epub 2017 Apr 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Prostaglandin e receptor activity
- Specific Function
- Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. The subsequent raise in intracellular cAMP is responsible for the ...
- Gene Name
- PTGER2
- Uniprot ID
- P43116
- Uniprot Name
- Prostaglandin E2 receptor EP2 subtype
- Molecular Weight
- 39759.945 Da
References
- Lindegaard Pedersen M, Kruger M, Grimm D, Infanger M, Wehland M: The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. Basic Clin Pharmacol Toxicol. 2019 Aug 12. doi: 10.1111/bcpt.13305. [Article]
- Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P: The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med. 2017 Jun;11(6):491-503. doi: 10.1080/17476348.2017.1317599. Epub 2017 Apr 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Prostaglandin j receptor activity
- Specific Function
- Receptor for prostaglandin D2 (PGD2). The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobiliza...
- Gene Name
- PTGDR
- Uniprot ID
- Q13258
- Uniprot Name
- Prostaglandin D2 receptor
- Molecular Weight
- 40270.11 Da
References
- Lindegaard Pedersen M, Kruger M, Grimm D, Infanger M, Wehland M: The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension. Basic Clin Pharmacol Toxicol. 2019 Aug 12. doi: 10.1111/bcpt.13305. [Article]
- Del Pozo R, Hernandez Gonzalez I, Escribano-Subias P: The prostacyclin pathway in pulmonary arterial hypertension: a clinical review. Expert Rev Respir Med. 2017 Jun;11(6):491-503. doi: 10.1080/17476348.2017.1317599. Epub 2017 Apr 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Zinc ion binding
- Specific Function
- Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
- Gene Name
- PPARD
- Uniprot ID
- Q03181
- Uniprot Name
- Peroxisome proliferator-activated receptor delta
- Molecular Weight
- 49902.99 Da
References
- Ali FY, Egan K, FitzGerald GA, Desvergne B, Wahli W, Bishop-Bailey D, Warner TD, Mitchell JA: Role of prostacyclin versus peroxisome proliferator-activated receptor beta receptors in prostacyclin sensing by lung fibroblasts. Am J Respir Cell Mol Biol. 2006 Feb;34(2):242-6. Epub 2005 Oct 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Agonist
- Curator comments
- The resource suggests that treprostinil inhibits platelet activation following a mechanism similar to the one promoted by anti-P2Y12 molecules. However, an interaction between treprostinil and P2Y12 remains to be validated.
- 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
- Bacha NC, Levy M, Guerin CL, Le Bonniec B, Harroche A, Szezepanski I, Renard JM, Gaussem P, Israel-Biet D, Boulanger CM, Smadja DM: Treprostinil treatment decreases circulating platelet microvesicles and their procoagulant activity in pediatric pulmonary hypertension. Pediatr Pulmonol. 2019 Jan;54(1):66-72. doi: 10.1002/ppul.24190. Epub 2018 Nov 28. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Treprostinil is primarily metabolized by CYP2C8.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- FDA Approved Drug Products: TYVASO (treprostinil) inhalation solution, for oral inhalation use [Link]
- FDA Approved Drug Products: REMODULIN (treprostinil) injection, for subcutaneous or intravenous use [Link]
- FDA Approved Drug Products: ORENITRAM (treprostinil) extended-release tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Gotzkowsky SK, Dingemanse J, Lai A, Mottola D, Laliberte K: Lack of a pharmacokinetic interaction between oral treprostinil and bosentan in healthy adult volunteers. J Clin Pharmacol. 2010 Jul;50(7):829-34. doi: 10.1177/0091270009351173. Epub 2010 Feb 4. [Article]
- FDA Approved Drug Products: ORENITRAM (treprostinil) extended-release tablets, for oral use [Link]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55