Details of the Drug

General Information of Drug (ID: DMTIQF3)

• Drug Name: Treprostinil
• Synonyms: Treprostinilo; Treprostinilum; Uniprost; Viveta; Treprostinil sodium; LRX 15; U 62840; Remodulin (TN); Treprostinil [USAN:INN]; UT-15; Treprostinil (USAN/INN); U-62,840; ((1R,2R,3aS,9aS)-2-hydroxy-1-((3S)-3-hydroxyoctyl)-2,3,3a,4,9,9a-hexahydro-1H-cylopent(b)naphthalen-5-yl)oxy)acetate; ({(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]naphthalen-5-yl}oxy)acetic acid; 15 AU81; 2-[[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid; 2-[[(1S,2S,3aR,9aR)-2-hydroxy-1-[(3R)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Pulmonary arterial hypertension	BB01.0	Approved	[1], [2]

• Therapeutic Class: Antihypertensive Agents
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 390.5
  Topological Polar Surface Area (xlogp); 4.5
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 5
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Bioavailability: The bioavailability of drug is 100% [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 10.7 mL/min/kg [5]
  Elimination: 4% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2 - 4 hours [5]
  Metabolism: The drug is metabolized via the liver [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 6.1456 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.09% [5]
  Vd: The volume of distribution (Vd) of drug is 14 L [7]
• Chemical Identifiers:
  Formula: C23H34O5
  IUPAC Name: 2-[[(1R,2R,3aS,9aS)-2-hydroxy-1-[(3S)-3-hydroxyoctyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[g]naphthalen-5-yl]oxy]acetic acid
  Canonical SMILES: CCCCC[C@@H](CC[C@H]1[C@@H](C[C@H]2[C@@H]1CC3=C(C2)C(=CC=C3)OCC(=O)O)O)O
  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
  InChIKey: PAJMKGZZBBTTOY-ZFORQUDYSA-N
• Cross-matching ID:
  PubChem CID: 6918140
  ChEBI ID: CHEBI:50861
  CAS Number: 81846-19-7
  DrugBank ID: DB00374
  TTD ID: D01WUA
  INTEDE ID: DR1632

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostacyclin receptor (PTGIR)	TTOFYT1	PI2R_HUMAN	Agonist	[8]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Substrate	[9]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[10]

Molecular Expression Atlas of This Drug

• The Studied Disease: Pulmonary arterial hypertension
• ICD Disease Classification: BB01.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostacyclin receptor (PTGIR)	DTT	PTGIR	7.12E-02	-0.13	-0.33
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	2.93E-03	-2.19E-01	-4.49E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	2.25E-03	-4.98E-01	-6.49E-01

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Treprostinil (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Cilostazol	DMZMSCT	Moderate	Increased risk of bleeding by the combination of Treprostinil and Cilostazol.	Arterial occlusive disease [BD40]	[36]
Linezolid	DMGFPU2	Moderate	Additive hypotensive effects by the combination of Treprostinil and Linezolid.	Bacterial infection [1A00-1C4Z]	[37]
Lapatinib	DM3BH1Y	Moderate	Decreased metabolism of Treprostinil caused by Lapatinib mediated inhibition of CYP450 enzyme.	Breast cancer [2C60-2C6Y]	[38]
Trastuzumab Emtansine	DMU1LXS	Moderate	Increased risk of bleeding by the combination of Treprostinil and Trastuzumab Emtansine.	Breast cancer [2C60-2C6Y]	[36]
Pentosan polysulfate	DM2HRKE	Moderate	Increased risk of bleeding by the combination of Treprostinil and Pentosan polysulfate.	Chronic pain [MG30]	[39]
Phenylbutazone	DMAYL0T	Moderate	Increased risk of bleeding by the combination of Treprostinil and Phenylbutazone.	Chronic pain [MG30]	[36]
Ketoprofen	DMRKXPT	Moderate	Increased risk of bleeding by the combination of Treprostinil and Ketoprofen.	Chronic pain [MG30]	[36]
Levomilnacipran	DMV26S8	Moderate	Increased risk of bleeding by the combination of Treprostinil and Levomilnacipran.	Chronic pain [MG30]	[40]
Anisindione	DM2C48U	Moderate	Increased risk of bleeding by the combination of Treprostinil and Anisindione.	Coagulation defect [3B10]	[36]
Regorafenib	DMHSY1I	Major	Increased risk of bleeding by the combination of Treprostinil and Regorafenib.	Colorectal cancer [2B91]	[41]
Ardeparin	DMYRX8B	Major	Increased risk of bleeding by the combination of Treprostinil and Ardeparin.	Coronary thrombosis [BA43]	[42]
Mifepristone	DMGZQEF	Moderate	Decreased metabolism of Treprostinil caused by Mifepristone mediated inhibition of CYP450 enzyme.	Cushing syndrome [5A70]	[43]
Lumacaftor	DMCLWDJ	Moderate	Increased metabolism of Treprostinil caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[44]
MK-8228	DMOB58Q	Moderate	Decreased metabolism of Treprostinil caused by MK-8228 mediated inhibition of CYP450 enzyme.	Cytomegaloviral disease [1D82]	[38]
Danaparoid	DM6CLBN	Major	Increased risk of bleeding by the combination of Treprostinil and Danaparoid.	Deep vein thrombosis [BD71]	[42]
Rivaroxaban	DMQMBZ1	Major	Increased risk of bleeding by the combination of Treprostinil and Rivaroxaban.	Deep vein thrombosis [BD71]	[45]
Sertraline	DM0FB1J	Moderate	Increased risk of bleeding by the combination of Treprostinil and Sertraline.	Depression [6A70-6A7Z]	[40]
Fluoxetine	DM3PD2C	Moderate	Increased risk of bleeding by the combination of Treprostinil and Fluoxetine.	Depression [6A70-6A7Z]	[40]
Vilazodone	DM4LECQ	Moderate	Increased risk of bleeding by the combination of Treprostinil and Vilazodone.	Depression [6A70-6A7Z]	[40]
Paroxetine	DM5PVQE	Moderate	Increased risk of bleeding by the combination of Treprostinil and Paroxetine.	Depression [6A70-6A7Z]	[40]
Selegiline	DM6034S	Moderate	Additive hypotensive effects by the combination of Treprostinil and Selegiline.	Depression [6A70-6A7Z]	[37]
Vortioxetine	DM6F1PU	Moderate	Increased risk of bleeding by the combination of Treprostinil and Vortioxetine.	Depression [6A70-6A7Z]	[40]
Duloxetine	DM9BI7M	Moderate	Increased risk of bleeding by the combination of Treprostinil and Duloxetine.	Depression [6A70-6A7Z]	[40]
Isocarboxazid	DMAF1NB	Moderate	Additive hypotensive effects by the combination of Treprostinil and Isocarboxazid.	Depression [6A70-6A7Z]	[37]
Milnacipran	DMBFE74	Moderate	Increased risk of bleeding by the combination of Treprostinil and Milnacipran.	Depression [6A70-6A7Z]	[40]
Escitalopram	DMFK9HG	Moderate	Increased risk of bleeding by the combination of Treprostinil and Escitalopram.	Depression [6A70-6A7Z]	[40]
Tranylcypromine	DMGB5RE	Moderate	Additive hypotensive effects by the combination of Treprostinil and Tranylcypromine.	Depression [6A70-6A7Z]	[37]
Desvenlafaxine	DMHD4PE	Moderate	Increased risk of bleeding by the combination of Treprostinil and Desvenlafaxine.	Depression [6A70-6A7Z]	[40]
Phenelzine	DMHIDUE	Moderate	Additive hypotensive effects by the combination of Treprostinil and Phenelzine.	Depression [6A70-6A7Z]	[37]
Clomipramine	DMINRKW	Moderate	Increased risk of bleeding by the combination of Treprostinil and Clomipramine.	Depression [6A70-6A7Z]	[40]
Heme	DMGC287	Moderate	Increased risk of bleeding by the combination of Treprostinil and Heme.	Discovery agent [N.A.]	[46]
Apigenin	DMI3491	Minor	Increased risk of bleeding by the combination of Treprostinil and Apigenin.	Discovery agent [N.A.]	[47]
PMID28870136-Compound-49	DMTUC9E	Moderate	Increased risk of bleeding by the combination of Treprostinil and PMID28870136-Compound-49.	Discovery agent [N.A.]	[36]
Fenfluramine	DM0762O	Moderate	Increased risk of bleeding by the combination of Treprostinil and Fenfluramine.	Epilepsy/seizure [8A61-8A6Z]	[40]
Phenobarbital	DMXZOCG	Moderate	Increased metabolism of Treprostinil caused by Phenobarbital mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[48]
Carbamazepine	DMZOLBI	Moderate	Increased metabolism of Treprostinil caused by Carbamazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[48]
Mefenamic acid	DMK7HFI	Moderate	Increased risk of bleeding by the combination of Treprostinil and Mefenamic acid.	Female pelvic pain [GA34]	[36]
Ripretinib	DM958QB	Moderate	Decreased metabolism of Treprostinil caused by Ripretinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[38]
Avapritinib	DMK2GZX	Major	Increased risk of bleeding by the combination of Treprostinil and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[41]
Sulfinpyrazone	DMEV954	Moderate	Increased risk of bleeding by the combination of Treprostinil and Sulfinpyrazone.	Gout [FA25]	[36]
Rifampin	DMA8J1G	Moderate	Increased metabolism of Treprostinil caused by Rifampin mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[49]
Rifapentine	DMCHV4I	Moderate	Increased metabolism of Treprostinil caused by Rifapentine mediated induction of CYP450 enzyme.	HIV-infected patients with tuberculosis [1B10-1B14]	[48]
Tipranavir	DM8HJX6	Major	Increased risk of bleeding by the combination of Treprostinil and Tipranavir.	Human immunodeficiency virus disease [1C60-1C62]	[50]
Gemfibrozil	DMD8Q3J	Moderate	Decreased metabolism of Treprostinil caused by Gemfibrozil mediated inhibition of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[38]
Teriflunomide	DMQ2FKJ	Moderate	Decreased metabolism of Treprostinil caused by Teriflunomide mediated inhibition of CYP450 enzyme.	Hyper-lipoproteinaemia [5C80]	[38]
Dipyridamole	DMXY30O	Moderate	Increased risk of bleeding by the combination of Treprostinil and Dipyridamole.	Hypertension [BA00-BA04]	[36]
Meclofenamic acid	DM05FXR	Moderate	Increased risk of bleeding by the combination of Treprostinil and Meclofenamic acid.	Inflammatory spondyloarthritis [FA92]	[36]
Acalabrutinib	DM7GCVW	Major	Increased risk of bleeding by the combination of Treprostinil and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[51]
Ibrutinib	DMHZCPO	Major	Increased risk of bleeding by the combination of Treprostinil and Ibrutinib.	Mature B-cell lymphoma [2A85]	[48]
Ponatinib	DMYGJQO	Major	Increased risk of bleeding by the combination of Treprostinil and Ponatinib.	Mature B-cell lymphoma [2A85]	[52]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Treprostinil caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[38]
Dabrafenib	DMX6OE3	Moderate	Increased metabolism of Treprostinil caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[48]
Panobinostat	DM58WKG	Major	Increased risk of bleeding by the combination of Treprostinil and Panobinostat.	Multiple myeloma [2A83]	[53]
Ozanimod	DMT6AM2	Moderate	Additive hypotensive effects by the combination of Treprostinil and Ozanimod.	Multiple sclerosis [8A40]	[37]
Fedratinib	DM4ZBK6	Moderate	Increased risk of bleeding by the combination of Treprostinil and Fedratinib.	Myeloproliferative neoplasm [2A20]	[36]
Dasatinib	DMJV2EK	Major	Increased risk of bleeding by the combination of Treprostinil and Dasatinib.	Myeloproliferative neoplasm [2A20]	[54]
Omacetaxine mepesuccinate	DMPU2WX	Major	Increased risk of bleeding by the combination of Treprostinil and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[39]
Prasugrel	DM7MT6E	Moderate	Increased risk of bleeding by the combination of Treprostinil and Prasugrel.	Myocardial infarction [BA41-BA43]	[36]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Treprostinil and Vorapaxar.	Myocardial infarction [BA41-BA43]	[36]
Tirofiban	DMQG17S	Moderate	Increased risk of bleeding by the combination of Treprostinil and Tirofiban.	Myocardial infarction [BA41-BA43]	[36]
Sibutramine	DMFJTDI	Moderate	Increased risk of bleeding by the combination of Treprostinil and Sibutramine.	Obesity [5B80-5B81]	[40]
Dexfenfluramine	DMJ7YDS	Moderate	Increased risk of bleeding by the combination of Treprostinil and Dexfenfluramine.	Obesity [5B80-5B81]	[40]
Diclofenac	DMPIHLS	Moderate	Increased risk of bleeding by the combination of Treprostinil and Diclofenac.	Osteoarthritis [FA00-FA05]	[36]
Nepafenac	DMYK490	Moderate	Increased risk of bleeding by the combination of Treprostinil and Nepafenac.	Osteoarthritis [FA00-FA05]	[55]
Naproxen	DMZ5RGV	Moderate	Increased risk of bleeding by the combination of Treprostinil and Naproxen.	Osteoarthritis [FA00-FA05]	[36]
MK-4827	DMLYGH4	Moderate	Increased risk of bleeding by the combination of Treprostinil and MK-4827.	Ovarian cancer [2C73]	[41]
Aspirin	DM672AH	Moderate	Increased risk of bleeding by the combination of Treprostinil and Aspirin.	Pain [MG30-MG3Z]	[36]
Etodolac	DM6WJO9	Moderate	Increased risk of bleeding by the combination of Treprostinil and Etodolac.	Pain [MG30-MG3Z]	[36]
Ibuprofen	DM8VCBE	Moderate	Increased risk of bleeding by the combination of Treprostinil and Ibuprofen.	Pain [MG30-MG3Z]	[36]
Nabumetone	DMAT2XH	Moderate	Increased risk of bleeding by the combination of Treprostinil and Nabumetone.	Pain [MG30-MG3Z]	[36]
Piroxicam	DMTK234	Moderate	Increased risk of bleeding by the combination of Treprostinil and Piroxicam.	Pain [MG30-MG3Z]	[36]
Safinamide	DM0YWJC	Moderate	Additive hypotensive effects by the combination of Treprostinil and Safinamide.	Parkinsonism [8A00]	[37]
Rasagiline	DM3WKQ4	Moderate	Additive hypotensive effects by the combination of Treprostinil and Rasagiline.	Parkinsonism [8A00]	[37]
Choline salicylate	DM8P137	Moderate	Increased risk of bleeding by the combination of Treprostinil and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[36]
Ketorolac	DMI4EL5	Moderate	Increased risk of bleeding by the combination of Treprostinil and Ketorolac.	Postoperative inflammation [1A00-CA43]	[36]
Bromfenac	DMKB79O	Moderate	Increased risk of bleeding by the combination of Treprostinil and Bromfenac.	Postoperative inflammation [1A00-CA43]	[36]
ABIRATERONE	DM8V75C	Moderate	Decreased metabolism of Treprostinil caused by ABIRATERONE mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[38]
Sorafenib	DMS8IFC	Moderate	Decreased metabolism of Treprostinil caused by Sorafenib mediated inhibition of CYP450 enzyme.	Renal cell carcinoma [2C90]	[38]
Salsalate	DM13P4C	Moderate	Increased risk of bleeding by the combination of Treprostinil and Salsalate.	Rheumatoid arthritis [FA20]	[36]
Meloxicam	DM2AR7L	Moderate	Increased risk of bleeding by the combination of Treprostinil and Meloxicam.	Rheumatoid arthritis [FA20]	[36]
Sulindac	DM2QHZU	Moderate	Increased risk of bleeding by the combination of Treprostinil and Sulindac.	Rheumatoid arthritis [FA20]	[36]
Oxaprozin	DM9UB0P	Moderate	Increased risk of bleeding by the combination of Treprostinil and Oxaprozin.	Rheumatoid arthritis [FA20]	[36]
Flurbiprofen	DMGN4BY	Moderate	Increased risk of bleeding by the combination of Treprostinil and Flurbiprofen.	Rheumatoid arthritis [FA20]	[36]
Fenoprofen	DML5VQ0	Moderate	Increased risk of bleeding by the combination of Treprostinil and Fenoprofen.	Rheumatoid arthritis [FA20]	[36]
Tolmetin	DMWUIJE	Moderate	Increased risk of bleeding by the combination of Treprostinil and Tolmetin.	Rheumatoid arthritis [FA20]	[36]
Salicyclic acid	DM2F8XZ	Moderate	Increased risk of bleeding by the combination of Treprostinil and Salicyclic acid.	Seborrhoeic dermatitis [EA81]	[36]
Warfarin	DMJYCVW	Moderate	Increased risk of bleeding by the combination of Treprostinil and Warfarin.	Supraventricular tachyarrhythmia [BC81]	[36]
Plicamycin	DM7C8YV	Moderate	Increased risk of bleeding by the combination of Treprostinil and Plicamycin.	Testicular cancer [2C80]	[36]
Caplacizumab	DMPUKA7	Moderate	Increased risk of bleeding by the combination of Treprostinil and Caplacizumab.	Thrombocytopenia [3B64]	[36]
Apixaban	DM89JLN	Major	Increased risk of bleeding by the combination of Treprostinil and Apixaban.	Thrombosis [DB61-GB90]	[41]
Cangrelor	DM8JRH0	Moderate	Increased risk of bleeding by the combination of Treprostinil and Cangrelor.	Thrombosis [DB61-GB90]	[36]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Treprostinil and Brilinta.	Thrombosis [DB61-GB90]	[41]
Clopidogrel	DMOL54H	Moderate	Increased risk of bleeding by the combination of Treprostinil and Clopidogrel.	Thrombosis [DB61-GB90]	[36]
Cabozantinib	DMIYDT4	Major	Increased risk of bleeding by the combination of Treprostinil and Cabozantinib.	Thyroid cancer [2D10]	[56]
Trimethoprim	DMM7CHK	Moderate	Decreased metabolism of Treprostinil caused by Trimethoprim mediated inhibition of CYP450 enzyme.	Urinary tract infection [GC08]	[38]
Betrixaban	DM2C4RF	Major	Increased risk of bleeding by the combination of Treprostinil and Betrixaban.	Venous thromboembolism [BD72]	[57]

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