Triflusal Both Platelet and Endothelial COX but Is Then Rap- a Viewpoint by José P

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Triflusal both platelet and endothelial COX but is then rap- A Viewpoint by José P. De La Cruz idly metabolised to HTB. Thus triflusal is elimi- Department of Pharmacology and nated from the blood, and endothelial cells can Therapeutics, School of Medicine, again produce prostacyclin; HTB does not affect University of Málaga, Málaga, Spain COX activity.[1] Supporting this, analysis of Inhibition of platelet activation constitutes the thromboxane and prostacyclin production 1 hour main pharmacological method of preventing after triflusal administration reveals that the former [2] thrombotic events in human arteries. Antiplatelet is inhibited and the latter preserved. agents are drugs that reduce thrombocyte activa- Moreover, HTB inhibits platelet aggregation in [3-5] tion through different mechanisms including the whole blood, by inhibiting cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) inhibition of thromboxane A2 synthesis: as this prostanoid induces platelet aggregation and vaso- and increasing intraplatelet cAMP content. Con- constriction, inhibiting it reduces the aggregatory versely, aspirin does not affect cAMP-PDE, and phenomenon. salicylic acid has no effects on either COX or Aspirin is an irreversible acetylator of cyclo- cAMP-PDE. oxygenase (COX) both in platelets (resulting in In conclusion, administration of triflusal con- decreased thromboxane production) and in the fers the activity of two different antiplatelet agents: endothelium (causing decreased prostacyclin syn- inhibition of COX (by triflusal itself) and stimula- thesis). Prostacyclin is a prostanoid that inhibits tion of cAMP (by HTB). These combined effects platelet aggregation and induces vasodilation; for are important in obtaining an optimal inhibition of this reason its inhibition is not recommended. platelet activity, particularly when both are present Triflusal is an antiplatelet agent which has been in the same drug. classed as an aspirin-like drug. Essential differ- ences between aspirin and triflusal were suggested References by some authors 15 years ago. Today it can be said 1. De La Cruz JP, Mata JM, Sanchez De La Cuesta F. Triflusal vs aspirin on the inhibition of human platelet and vascular that triflusal is not a specific type of aspirin but cyclooxygenase. Gen Pharmacol 1992; 23 (3):297-300 rather a completely different antiplatelet agent. 2. De La Cruz JP, Pavia J, Garcia-Arnes J, Sanchez De La Cuesta F. Effects of triflusal and acetylsalicylic acid on platelet ag- This statement is based on the different activities gregation in whole blood of diabetic patients. Eur J Haematol of 3-hydroxy-4-trifluoro-methylbenzoic acid 1988 Mar; 40:232-236 (HTB) and salicylic acid, which are the respective 3. De La Cruz JP, Pavia J, Bellido I, Gonzalez MC, Sanchez De La Cuesta F. Platelet antiaggregatory effect of triflusal in hu- metabolites of triflusal and aspirin. man whole blood. Meth Find Expl Clin Pharmacol 1988 Apr; Triflusal inhibits both platelet and endothelial 10:273-277 [1] 4. De La Cruz JP, Pavia J, Bellido I, Sanchez De La Cuesta F. COX. Recovery of COX activity in platelets re- Effect of triflusal and acetylsalicylic acid on platelet aggrega- quires total replacement of the cells to restore tion in human whole blood: influence of red blood cells and thromboxane production (platelets have no nu- leukocytes. Meth Find Expl Clin Pharmacol 1988 Apr; 10:363-367 clei); whereas, inhibition is reversible in endothe- 5. De La Cruz JP, Villalobos MA, Garcia PJ, Smith-Agreda JM, lial cells where only the absence of the drug is re- Sanchez De La Cuesta F. Effects of triflusal and its main metabolite HTB, on platelet interaction with subendothel- quired for restoration of prostacyclin synthesis. ium in healthy volunteers. Eur J Clin Pharmacol 1995; 47: After its absorption into the blood, triflusal inhibits 497-502