An analog of Aspirin; inhibits platelet aggregation. Antithrombotic.
Mechanism of action
2-hydroxy-4-trifluoromethylbenzoic acid (HTB), the deacetylated
metabolite of triflusal, retains significant antiplatelet activity. Triflusal is rapidly absorbed and
metabolized. The area under the concentration–time curve for triflusal is 20.26 mg/L/hour after a
900-mg dose, whereas that for HTB is 42.27 mg/L/hour. Much of the pharmacokinetic data for
triflusal activity is associated with HTB. The inhibition of COX, as measured by reduced production
of thromboxane B2, is 25% after 2 hours and 85% after 7 days with triflusal, whereas the effects of
aspirin on thromboxane B2 is more than 90% reduction after 2 hours and is maintained at this level
after 7 days. It would appear that the presence of a 4-trifluoromethyl group also greatly enhances triflusal's ability to inhibit the activation of nuclear factor κB, which in turn regulates the
expression of the mRNA of vascular
cell adhesion molecule-1 needed for platelet aggregation. In addition, triflusal increases nitric
oxide synthesis in neutrophils, which results in an increased vasodilatory potential. Finally, an
additional site of action for triflusal/HTB is the inhibition of cAMP phosphodiesterase, leading to
increased levels of cAMP. Elevated cAMP levels decrease platelet aggregation through decreased
mobilization of calcium. Aspirin and salicylic acid do not significantly increase cAMP levels.
Clinical Use
Triflusal (2-acetoxy-4-trifluoromethyl benzoic acid) is an antiplatelet drug that despite its structural
similarity to aspirin exhibits quite different pharmacological and pharmacokinetic
properties.
