TRIFLUSAL

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H7F3O4
Molecular Weight	248.1554
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)OC1=CC(=CC=C1C(O)=O)C(F)(F)F

InChI

InChIKey=RMWVZGDJPAKBDE-UHFFFAOYSA-N

InChI=1S/C10H7F3O4/c1-5(14)17-8-4-6(10(11,12)13)2-3-7(8)9(15)16/h2-4H,1H3,(H,15,16)

HIDE SMILES / InChI

Molecular Formula	C10H7F3O4
Molecular Weight	248.1554
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16939630
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/triflusal.html | https://www.drugbank.ca/drugs/DB08814 | https://www.ncbi.nlm.nih.gov/pubmed/19465361 | https://www.ncbi.nlm.nih.gov/pubmed/19641312

Triflusal (trade names Disgren, Grendis, Aflen, Triflux, ets) is a member of the salicylate family with a well-established platelet aggregation inhibitory profile that differs from that of acetylsalicylic acid (ASA) in its pharmacokinetic and pharmacodynamic properties. Triflusal irreversibly inhibits cyclooxygenase-1 through its potency is lower than that of acetylsalicylic acid (ASA). Triflusal shows potent inhibition of vascular prostacyclin synthesis, and weak inhibition of platelet phosphodiesterase. Triflusal also favors the production of NO and increases the concentration of cyclic nucleotides. A number of experimental and clinical studies have shown that triflusal is a potentially useful choice in the treatment and prophylaxis of brain ischemia because of its antithrombogenic as well as neuroprotective effects. Triflusal anti-thrombogenic properties have been demonstrated clinically and experimentally, while its neuroprotective effects have been shown only in animal models. Triflusal is administered orally. It Is absorbed primarily in the small intestines and its bioavailability in humans ranges from 83% to 100%. Once absorbed, 99% of triflusal binds to plasma proteins in experimental animals as well as in humans. Triflusal readily crosses organic barriers, but its blood levels are always higher than tissue levels. Upon passage through the liver, triflusal is deacetylated, forming 2-hydroxy-4-trifluoro-methyl-benzoicacid (HTB) as the main active metabolite. Triflusal inhibits platelet aggregation and interaction of platelets with subendothelium. The antiplatelet effect of triflusal has been documented in experimental animals and in humans, in in vitro and ex vivo studies, and in in vivo models of thrombogenesis in animals. Triflusal inhibited collagen- or arachidonic acid-induced platelet aggregation in platelet-rich plasma more effectively than ADP-induced platelet aggregation. Independently of its antithrombotic effect, triflusal acts directly on the nervous tissue to reduce the damage caused by ischemic or cytotoxic insults. The daily oral intake of 600 mg triflusal led to HTB levels in the cerebrospinal fluid that had neuroprotective effects in experimental animals. Traditionally, antiplatelet drugs have been associated with an increased risk of bleeding complications.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cyclooxygenase-1 131 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19465361	Inhibitor 8504
Nitric-oxide synthase, endothelial 19 Target ID: CHEMBL4803 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19465361	Activator 1447
Nitric oxide synthase, inducible 55 Target ID: CHEMBL4481 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16939630	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Cerebral infarction 14 Sources: https://clinicaltrials.gov/ct2/show/NCT01174693	Primary	Approved 8583	Disgren Approved Use Unknown
Prevention of atherothrombosis in patients with stable coronary artery disease 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24503927	Preventing	Approved 8583	Disgren Approved Use Unknown
Acute ischemic stroke 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19641312	Primary	Approved 8583	Disgren Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
88.61 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20184225/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		2‐HYDROXY‐4‐TRIFLUOROMETHYLBENZOIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
4471.33 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20184225/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		2‐HYDROXY‐4‐TRIFLUOROMETHYLBENZOIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
48.67 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20184225/	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		2‐HYDROXY‐4‐TRIFLUOROMETHYLBENZOIC ACID plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	Other AEs: Gastrointestinal disorders, Central and peripheral nervous system disorders... Other AEs: Gastrointestinal disorders (some serious, 26.8%) Central and peripheral nervous system disorders (8.9%) Body disorders (5.5%) Respiratory system disorders (3.8%) Platelet bleeding and clotting disorders (1.4%) Skin and appendage disorders (1.5%) Hearing and vestibular disorders (1.2%) Bleeding events (2.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
600 mg 1 times / day steady-state, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady-state Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/	Other AEs: Gastrointestinal discomfort... Other AEs: Gastrointestinal discomfort (mild, 30%) Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/
900 mg single, oral Highest studied dose\|Studied dose Dose: 900 mg Route: oral Route: single Dose: 900 mg Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/	Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/

AEs

AE	Significance	Dose	Population
Hearing and vestibular disorders	1.2%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Platelet bleeding and clotting disorders	1.4%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Skin and appendage disorders	1.5%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Bleeding events	2.4%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Respiratory system disorders	3.8%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Body disorders	5.5%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Central and peripheral nervous system disorders	8.9%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Gastrointestinal disorders	some serious, 26.8%	600 mg 1 times / day steady, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/10681486/
Gastrointestinal discomfort	mild, 30%	600 mg 1 times / day steady-state, oral Highest studied dose\|Studied dose Dose: 600 mg, 1 times / day Route: oral Route: steady-state Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: M F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/24105106/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 inducer 1087	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 429 CYP2C19 2057 CYP1A2 2153 P-gp 1741	P-gp 2052 CYP 303

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results	inconclusive [IC50 21.3174 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzMzIwMzIifX0=	inconclusive [IC50 3.9811 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results Page: 3.0	inconclusive
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results Page: 1.0	no [IC50 9.5221 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDEzMzIwMzIifX0=	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTMzMjAzMiJ9fQ==	no [IC50 >10 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results Page: 63.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results Page: 67.0	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 303	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29037010/	no
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results Page: 66 \|69	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/9458#section=BioAssay-Results Page: 44.0

PubMed

Title	Date	PubMed
Addressing the challenges to successful recruitment and retention in Alzheimer's disease clinical trials.	2010-12-21	21172069
Triflusal reduces cerebral ischemia induced inflammation in a combined mouse model of Alzheimer's disease and stroke.	2010-12-17	20934412
Bioactive polymeric systems with platelet antiaggregating activity for the coating of vascular devices.	2010-10-11	20866066
Is there an association between low dose aspirin and anemia (without overt bleeding)? Narrative review.	2010-09-29	20920233
Oral antiplatelet therapy in stroke prevention. Minireview.	2010-09	21048805
Electrochemical behavior of triflusal, aspirin and their metabolites at glassy carbon and boron doped diamond electrodes.	2010-08	20402644
Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis.	2010-06-16	20553581
Prevention strategies for cardioembolic stroke: present and future perspectives.	2010-06-15	20721324
Thrombi of different pathologies: implications for diagnosis and treatment.	2010-06	20842548
Update on antithrombotic therapy for stroke prevention in atrial fibrillation.	2010-06	20461116
Thinking outside the box about COX-1 in Alzheimer's disease.	2010-06	20206264
Triflusal reduces dense-core plaque load, associated axonal alterations and inflammatory changes, and rescues cognition in a transgenic mouse model of Alzheimer's disease.	2010-06	20149872
In vitro and in vivo performance of a dual drug-eluting stent (DDES).	2010-05	20189244
Study on QSTR of benzoic acid compounds with MCI.	2010-03-24	20480017
Influence of antiplatelet pre-treatment on the risk of intracranial haemorrhage in acute ischaemic stroke after intravenous thrombolysis.	2010-02	19912320
Staging anti-inflammatory therapy in Alzheimer's disease.	2010	21152343
Are NSAIDs useful to treat Alzheimer's disease or mild cognitive impairment?	2010	20725517
Eicosanoids in the innate immune response: TLR and non-TLR routes.	2010	20689730
Presenilin/gamma-Secretase and Inflammation.	2010	20559464
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.	2010	20184225
Comparison of triple antiplatelet therapy including triflusal and conventional dual therapy in patients who underwent drug-eluting stent implantation.	2009-11	19952467
The short-term effect on restenosis and thrombosis of a cobalt-chromium stent eluting two drugs in a porcine coronary artery model.	2009-10	19627432
Long-term follow-up of atrial fibrillation patients in the NASPEAF study. Prospective evaluation of different antiplatelet treatments.	2009-09	19712620
Photonucleophilic addition of the epsilon-amino group of lysine to a triflusal metabolite as a mechanistic key to photoallergy mediated by the parent drug.	2009-07	19462393
Neuroprotective effects of the anti-inflammatory compound triflusal on ischemia-like neurodegeneration in mouse hippocampal slice cultures occur independent of microglia.	2009-07	19341733
Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness.	2009-05-26	19465361
[Resistance to triflusal or an insufficient dose?].	2009-04-03	19340787
Effect of age on stroke prevention therapy in patients with atrial fibrillation: the atrial fibrillation investigators.	2009-04	19182090
Triflusal and aspirin have different effects on inflammatory biomarkers measured in patients with acute ischemic stroke.	2009	19641312
Mechanism-based treatments for Alzheimer's disease.	2009	19585951
Inflammaging as a prodrome to Alzheimer's disease.	2008-11-11	19014446
Protective effects of triflusal on secondary thrombus growth and vascular cyclooxygenase-2.	2008-08	18503633
Salicylates increase insulin secretion in healthy obese subjects.	2008-07	18460568
A randomized, double-blind, placebo controlled-trial of triflusal in mild cognitive impairment: the TRIMCI study.	2008-03-05	18317243
The inflammatory hypothesis of Alzheimer disease: dead or alive?	2008-03-05	18317241
Spectroscopic and chromatographic characterization of triflusal delivery systems prepared by using supercritical impregnation technologies.	2008-02-13	18093783
Safety of triflusal (antiplatelet drug) in patients with aspirin-exacerbated respiratory diseases.	2008-01	18053020
Bioequivalence of two oral formulations of triflusal capsules in healthy volunteers.	2008	18677970
Use of aspirin for primary and secondary prevention of cardiovascular disease in diabetic patients in an ambulatory care setting in Spain.	2007-10-17	17941978
Amiodarone-induced hepatitis and polyneuropathy.	2007-09	17939344
[Trend in platelet antiaggregants utilization in the autonomous community of Valencia, Spain (2000-2005)].	2007-08-19	17694635
The study of the influence of surfactant charge on alkaline hydrolysis reactions of acetylsalicylic acid (ASA) and triflusal (TFL) using spectrophotometric methods.	2007-07	17498930
Effects of triflusal and aspirin in a rat model of cerebral ischemia.	2007-02	17194886
Antithrombotic treatment in atrial fibrillation.	2006-09	16907647
Antithrombotic treatment in atrial fibrillation. Response to: Bereznicki LR, Peterson GM, Jackson SL, Jeffrey EC: the risks of warfarin use in the elderly. Expert Opin. Drug Saf. (2006) 5(3):417-431.	2006-07	16774485
Platelet microparticles and platelet adhesion: therapeutic implications for the prevention and treatment of stroke.	2006-05	16635445
Platelet aggregation inhibitors in primary and secondary prevention of ischemic stroke.	2006-04-11	21289960
Triflusal: an antiplatelet drug with a neuroprotective effect?	2006	16939630
Triflusal: a review of its use in cerebral infarction and myocardial infarction, and as thromboprophylaxis in atrial fibrillation.	2006	16620146
Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (TRAC): rationale and design for a prospective, randomized, co-operative trial.	2003-06	17670019

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dosage in adults is 600-900 mg/day, administered as a single dose of 600 mg or in two or three doses of 300 mg, preferably during or after meals.

Route of Administration: Oral

In Vitro Use Guide

Platelet rich plasma (500 mkL) was incubated at 37C for 3 min in the aggregometer with continuous stirring (1000 rpm) and then stimulated with submaximal concentrations . of thrombin (0.025 U/ml) or ADP (1 mkM). Before stimulation, 100 mkl of the neutrophil suspension was added to plasma rich plasma to reach a final amount of 1.25x10^8 platelets and 1x10^6 neutrophils (125:1) which approximate the relative concentrations in normal blood. In other series of experiments, increasing neutrophil concentrations ranging from 10^6 to 10^7 cells/ml were added to 1.25x10^8 platelets. Acetylsalicylic acid or triflusal were added to the platelet–neutrophil suspension 5 min before platelet stimulation with thrombin or ADP

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:02:24 GMT 2025` Edited by `admin` on `Mon Mar 31 18:02:24 GMT 2025`
Record UNII	1Z0YFI05OO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TRIFLUSAL

Official Name

English

TRIFLUSAL [MI]

Preferred Name

English

TRIFLUSAL [EP MONOGRAPH]

Common Name

English

TRIFLUSAL [MART.]

Common Name

English

triflusal [INN]

Common Name

English

Triflusal [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QB01AC18