Platelet antiaggregatory effect of triflusal in human whole blood.
An in vitro and ex vivo study has been made to determine the inhibition of platelet aggregation in human whole blood (WB) and platelet rich plasma by triflusal and its main metabolite HTB (2-hydroxy-4-trifluoromethylbenzoic acid). Triflusal was administered orally at 300 mg x 2/day, for 15 days, to 13 healthy volunteers (ex vivo tests). Triflusal and HTB, at concentrations lower than 1 mM, produced a significant inhibition of platelet aggregation induced by ADP (2.5 microM, final) and collagen (1 microgram/ml, final) in PRP, while about 50% inhibition was induced in WB samples at 0.12 mM. Ex vivo studies also revealed a stronger inhibitory effect of triflusal in WB samples against several inducers; differences were particularly pronounced against ADP (10.6 times more potent in WB). These results suggest an important role of red blood cells and/or leukocytes in the mechanism of action of triflusal. The antiplatelet effect of triflusal in WB was modified when incubated with HTB at therapeutic concentrations. The IC50 value against collagen increased from 82 to 140 microM with 37.5 microM HTB, but decreased in a dose-dependent manner when incubated with higher concentrations of HTB, suggesting that inhibition of platelet cyclooxygenase by HTB masks its negative interaction with triflusal.
de la Cruz
J P
JP
Department of Pharmacology and Therapeutics, School of Medicine, University of Malaga, Spain.
Pavia
J
J
Bellido
I
I
González
M C
MC
Sánchez de la Cuesta
F
F
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D003094:Collagen / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000097:blood
D010975:Platelet Aggregation Inhibitors; D012459:Salicylates; C016167:triflusal; C033502:4-trifluoromethylsalicylic acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D003094:Collagen; D004837:Epinephrine