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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
SynonymLanguageCode
SID11112328Not AvailableNot Available
TriflusalNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
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
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
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

Targets

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

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