Welcome to DrugBank 4.0! If you prefer, you can still go back to version 3.0.
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
SynonymsNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS numberNot Available
WeightNot Available
Chemical FormulaNot Available
InChI KeyNot Available
InChINot Available
IUPAC NameNot Available
SMILESNot Available
Mass SpecNot Available
Taxonomy
KingdomNot Available
SuperclassNot Available
ClassNot Available
SubclassNot Available
Direct parentNot Available
Alternative parentsNot Available
SubstituentsNot Available
Classification descriptionNot Available
Pharmacology
Indication
  • Prevention of cardiovascular events such as stroke
  • Acute treatment of cerebral infarction, myocardial infarction
  • 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.
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
    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
    Property Value Probability
    Human Intestinal Absorption Not Available Not Available
    Blood Brain Barrier Not Available Not Available
    Caco-2 permeable Not Available Not Available
    P-glycoprotein substrate Not Available Not Available
    P-glycoprotein inhibitor I Not Available Not Available
    P-glycoprotein inhibitor II Not Available Not Available
    Renal organic cation transporter Not Available Not Available
    CYP450 2C9 substrate Not Available Not Available
    CYP450 2D6 substrate Not Available Not Available
    CYP450 3A4 substrate Not Available Not Available
    CYP450 1A2 substrate Not Available Not Available
    CYP450 2C9 substrate Not Available Not Available
    CYP450 2D6 substrate Not Available Not Available
    CYP450 2C19 substrate Not Available Not Available
    CYP450 3A4 substrate Not Available Not Available
    CYP450 inhibitory promiscuity Not Available Not Available
    Ames test Not Available Not Available
    Carcinogenicity Not Available Not Available
    Biodegradation Not Available Not Available
    Rat acute toxicity Not Available Not applicable
    hERG inhibition (predictor I) Not Available Not Available
    hERG inhibition (predictor II) Not Available Not Available
    Pharmacoeconomics
    ManufacturersNot Available
    PackagersNot Available
    Dosage forms
    FormRouteStrength
    CapsuleOral300mg
    CapsuleOral600mg
    PricesNot Available
    PatentsNot Available
    Properties
    Statesolid
    Experimental PropertiesNot Available
    Predicted PropertiesNot Available
    Spectra
    SpectraNot Available
    References
    Synthesis ReferenceNot Available
    General Reference
    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
    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. Pubmed
    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. Epub 2008 May 22. Pubmed
    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. Pubmed
    5. Costa J, Ferro JM, Matias-Guiu J, Alvarez-Sabin J, Torres F: Triflusal for Preventing Serious Vascular Events in People at High Risk. Stroke. 2006 Jun 22. Pubmed
    6. 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
    7. 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
    8. 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
    9. 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
    10. 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
    External Links
    ResourceLink
    ATC CodesB01AC18
    AHFS CodesNot Available
    PDB EntriesNot Available
    FDA labelNot Available
    MSDSNot Available
    Interactions
    Drug Interactions
    Drug
    IbuprofenThe metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of ibuprofen to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.
    NaproxenThe metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of naproxen to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.
    PiroxicamThe metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of glisentide to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.
    WarfarinThe metabolite of triflusal, 2-hydroxy-4-trifluoro-methyl-benzoic acid (HTB), impairs the serum protein binding of warfarin to the same extent as acetylsalisylic acid. Thus, the free fraction of glisentide may be increased. A dosage reduction may be required if used in combination.
    Food Interactions
    • Gingko bilboa
    • Herbs with anticoagulant/antiplatelet activity such as alfalfa, feverfew, ginger, ginseng, grape seed, green tea, horseradish

    1. Prostaglandin G/H synthase 1

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Prostaglandin G/H synthase 1 P23219 Details

    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
    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

    2. Nuclear factor NF-kappa-B p105 subunit

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Nuclear factor NF-kappa-B p105 subunit P19838 Details

    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
    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
    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. Pubmed
    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

    3. Nitric oxide synthase, inducible

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: agonist

    Components

    Name UniProt ID Details
    Nitric oxide synthase, inducible P35228 Details

    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
    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
    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
    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

    4. cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A Q9Y233 Details

    References:

    1. McNeely W, Goa KL: Triflusal. Drugs. 1998 Jun;55(6):823-33; discussion 834-5. Pubmed
    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

    Comments
    Drug created on June 28, 2011 23:05 / Updated on July 03, 2011 09:33