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Identification
NameTriflusal
Accession NumberDB08814
TypeSmall Molecule
GroupsApproved
Description

Approved by the European Stroke Organization, triflusal is recommended as lone therapy for the secondary prevention of atheroembotic stroke. Triflusal appears to be equally effective with a better safety profile than acetylsalicylic acid plus dypridamole and clopidogrel alone based on a double blind, randomized TACIP and TAPIRSS trials.

Structure
Thumb
Synonyms
Triflusal
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII1Z0YFI05OO
CAS numberNot Available
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Taxonomy
ClassificationNot classified
Pharmacology
IndicationFor the pevention of cardiovascular events such as stroke, for acute treatment of cerebral infarction, myocardial infarction, and for thromboprophylaxis due to atrial fibrillation.
PharmacodynamicsTriflusal is an antithrombotic anticoagulant. It irreversibly inhibits the production of thromboxane-B2 in platelets by acetylating cycloxygenase-1. Triflusal affects many other targets such as NF kappa B, which is a gene expression regulatory factor for cycloxygenase-a and cytokines. Numerous studies comparing the efficacy and safety profile (i.e. systemic hemorrhage) between triflusal and acetylsalsylic acid has shown either no significant difference or a better effacy and safety profile for triflusal. Triflusal has been shown to protect cerebral tissue due to its inhibition of lipid peroxidation resulting from anoxia-reoxygenation.
Mechanism of actionTriflusal is chemically related to acetylsalicylic acid (ASA) and irreversibly inhibits cycloxygenase-1 (COX-1) in platelets. Acetylation of the active group of COX-1 prevents the formation of thromboxane-B2 in platelets. However, it is unique because it spares the arachidonic acid metabolic pathway in endothelial cells. In addition, it favors the production of nitric oxide, a vasodilator.
Related Articles
AbsorptionAbsorbed in the small intestine with a bioavailability range from 83% to 100%. There is no significant difference between the absorption of the oral solution and capsule formulation.
Volume of distribution

34L

Protein bindingBinds to plasma proteins almost entirely (99%)
Metabolism

In the liver, triflusal undergoes deacetylation, forming its main metabolite 2-OH-4-trifluoromethyl benzoic acid (HTB).

SubstrateEnzymesProduct
Triflusal
Not Available
2-hydroxy-4-trifluoromethyl benzoic acidDetails
Route of eliminationPrimarily renal.
Half lifeIn healthy human, the half life is 0.5 +/- 0.1h, while that of HTB is 34.3 +/- 5.3h.
Clearance

Renal clearance is 0.8 +/- 0.2L/h and 0.18 +/1 0.04L/h for triflusal and HTB, respectively.

ToxicityExcessive bleeding. The risk of bleeding is less than that of acetylsalicylic acid.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted PropertiesNot Available
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
References
Synthesis ReferenceNot Available
General References
  1. Anninos H, Andrikopoulos G, Pastromas S, Sakellariou D, Theodorakis G, Vardas P: Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness. Hellenic J Cardiol. 2009 May-Jun;50(3):199-207. [PubMed:19465361 ]
  2. Izquierdo I, Borja J, Rovira S, Pelagio P, Torres F, Cebrecos J, Garcia-Rafanell J: Comparative bioavailability study of triflusal oral solution vs. triflusal capsules in healthy subjects. A single, randomized, two-way cross-over, open-label phase I study. Arzneimittelforschung. 2010;60(1):36-41. doi: 10.1055/s-0031-1296246. [PubMed:20184225 ]
  3. Duran X, Sanchez S, Vilahur G, Badimon L: Protective effects of triflusal on secondary thrombus growth and vascular cyclooxygenase-2. J Thromb Haemost. 2008 Aug;6(8):1385-92. doi: 10.1111/j.1538-7836.2008.03036.x. Epub 2008 May 22. [PubMed:18503633 ]
  4. Quetglas EG, Campanero MA, Sadaba B, Escolar M, Azanza JR: Bioequivalence of two oral formulations of triflusal capsules in healthy volunteers. Arzneimittelforschung. 2008;58(6):283-7. doi: 10.1055/s-0031-1296508. [PubMed:18677970 ]
  5. Gonzalez-Correa JA, De La Cruz JP: Triflusal: an antiplatelet drug with a neuroprotective effect? Cardiovasc Drug Rev. 2006 Spring;24(1):11-24. [PubMed:16939630 ]
  6. Fraj J, Valero A, Vives R, Perez I, Borja J, Izquierdo I, Picado C: Safety of triflusal (antiplatelet drug) in patients with aspirin-exacerbated respiratory diseases. Allergy. 2008 Jan;63(1):112-5. [PubMed:18053020 ]
  7. Sanchez-Machin I, Garcia Robaina JC, Torre Morin F: Widespread eczema from triflusal confirmed by patch testing. Contact Dermatitis. 2004 Apr;50(4):257. [PubMed:15186390 ]
  8. Matias-Guiu J, Ferro JM, Alvarez-Sabin J, Torres F, Jimenez MD, Lago A, Melo T: Comparison of triflusal and aspirin for prevention of vascular events in patients after cerebral infarction: the TACIP Study: a randomized, double-blind, multicenter trial. Stroke. 2003 Apr;34(4):840-8. Epub 2003 Mar 20. [PubMed:12649515 ]
  9. Culebras A, Rotta-Escalante R, Vila J, Dominguez R, Abiusi G, Famulari A, Rey R, Bauso-Tosselli L, Gori H, Ferrari J, Reich E: Triflusal vs aspirin for prevention of cerebral infarction: a randomized stroke study. Neurology. 2004 Apr 13;62(7):1073-80. [PubMed:15079004 ]
  10. Costa J, Ferro JM, Matias-Guiu J, Alvarez-Sabin J, Torres F: Triflusal for preventing serious vascular events in people at high risk. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD004296. [PubMed:16034926 ]
External Links
ATC CodesB01AC18
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Prostaglandin-endoperoxide synthase activity
Specific Function:
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
Molecular Weight:
68685.82 Da
References
  1. Anninos H, Andrikopoulos G, Pastromas S, Sakellariou D, Theodorakis G, Vardas P: Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness. Hellenic J Cardiol. 2009 May-Jun;50(3):199-207. [PubMed:19465361 ]
  2. Dominguez MJ, Vacas M, Saez Y, Olabarria I, Velasco A, Iriarte JA, Forn J: Effects of triflusal in patients with prosthetic heart valves. Clin Ther. 1985;7(3):357-60. [PubMed:3838919 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Transcriptional repressor activity, rna polymerase ii transcription regulatory region sequence-specific binding
Specific Function:
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-co...
Gene Name:
NFKB1
Uniprot ID:
P19838
Molecular Weight:
105355.175 Da
References
  1. Zhang W, Potrovita I, Tarabin V, Herrmann O, Beer V, Weih F, Schneider A, Schwaninger M: Neuronal activation of NF-kappaB contributes to cell death in cerebral ischemia. J Cereb Blood Flow Metab. 2005 Jan;25(1):30-40. [PubMed:15678110 ]
  2. Anninos H, Andrikopoulos G, Pastromas S, Sakellariou D, Theodorakis G, Vardas P: Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness. Hellenic J Cardiol. 2009 May-Jun;50(3):199-207. [PubMed:19465361 ]
  3. Gomez-Isla T, Blesa R, Boada M, Clarimon J, Del Ser T, Domenech G, Ferro JM, Gomez-Anson B, Manubens JM, Martinez-Lage JM, Munoz D, Pena-Casanova J, Torres F: A randomized, double-blind, placebo controlled-trial of triflusal in mild cognitive impairment: the TRIMCI study. Alzheimer Dis Assoc Disord. 2008 Jan-Mar;22(1):21-9. doi: 10.1097/WAD.0b013e3181611024. [PubMed:18317243 ]
  4. Whitehead SN, Bayona NA, Cheng G, Allen GV, Hachinski VC, Cechetto DF: Effects of triflusal and aspirin in a rat model of cerebral ischemia. Stroke. 2007 Feb;38(2):381-7. Epub 2006 Dec 28. [PubMed:17194886 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Tetrahydrobiopterin binding
Specific Function:
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-n...
Gene Name:
NOS2
Uniprot ID:
P35228
Molecular Weight:
131116.3 Da
References
  1. Anninos H, Andrikopoulos G, Pastromas S, Sakellariou D, Theodorakis G, Vardas P: Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness. Hellenic J Cardiol. 2009 May-Jun;50(3):199-207. [PubMed:19465361 ]
  2. Sanchez de Miguel L, Casado S, Farre J, Garcia-Duran M, Rico LA, Monton M, Romero J, Bellver T, Sierra MP, Guerra JI, Mata P, Esteban A, Lopez-Farre A: Comparison of in vitro effects of triflusal and acetysalicylic acid on nitric oxide synthesis by human neutrophils. Eur J Pharmacol. 1998 Feb 5;343(1):57-65. [PubMed:9551715 ]
  3. De Miguel LS, Jimenez A, Monton M, Farre J, Del Mar Arriero M, Rodriguez-Feo JA, Garcia-Canete J, Rico L, Gomez J, Nunez A, Casado S, Farre AL: A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet function. Eur J Clin Invest. 2000 Sep;30(9):811-7. [PubMed:10998082 ]
  4. Gonzalez-Correa JA, De La Cruz JP: Triflusal: an antiplatelet drug with a neuroprotective effect? Cardiovasc Drug Rev. 2006 Spring;24(1):11-24. [PubMed:16939630 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Metal ion binding
Specific Function:
Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate.
Gene Name:
PDE10A
Uniprot ID:
Q9Y233
Molecular Weight:
88411.71 Da
References
  1. McNeely W, Goa KL: Triflusal. Drugs. 1998 Jun;55(6):823-33; discussion 834-5. [PubMed:9617597 ]
  2. De Miguel LS, Jimenez A, Monton M, Farre J, Del Mar Arriero M, Rodriguez-Feo JA, Garcia-Canete J, Rico L, Gomez J, Nunez A, Casado S, Farre AL: A 4-trifluoromethyl derivative of salicylate, triflusal, stimulates nitric oxide production by human neutrophils: role in platelet function. Eur J Clin Invest. 2000 Sep;30(9):811-7. [PubMed:10998082 ]
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Drug created on June 28, 2011 23:05 / Updated on April 12, 2016 21:01