Skip to main content
Log in

Effects of triflusal and its main metabolite HTB on platelet interaction with subendothelium in healthy volunteers

  • Pharmacodynamics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

The ex vivo effect of triflusal and acetylsalicylic acid (ASA) on platelet interaction with the subendothelium using the Baumgartner perfusion system (wall shear rate 350 s−1) was assessed in blood from 10 healthy volunteers who given a 15-day course of triflusal 600 mg per day and ASA 400 mg per day in a crossover trial.

The percentage of platelets on the subendothelium showed a decrease of 62% in samples from subjects on ASA and a decrease of 93% in those from subjects on triflusal (P<0.005). The percentage of the subendothelial surface covered by platelets was reduced by 23.3% after treatment with ASA, mainly due to inhibition of aggregates (75.2%), and by 29.9% after treatment with triflusal, mainly due to inhibition of aggregates (89.6%) and of adhesion (25%). The subendothelial surface covered by activated platelets (adhesions and thrombi) showed 32.5% inhibition after treatment with triflusal and 11.6% after treatment with ASA (P<0.043 vs. triflusal). In the in vitro experiments, 10 μmol·l−1 triflusal did not modify the percentage of the subendothelium covered by platelets. HTB 1 mmol·l−1 inhibited adhesion (26%) and aggregates (18%).

We conclude that HTB participates in the ex vivo effects of triflusal on the platelet-subendothelium interaction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. García-Rafanell J, Planas J, Puig-Parellada P (1979) Comparison of the inhibitory effect of acetylsalicylic acid and triflusal on enzymes related to thrombosis. Arch Int Pharmacodyn Ther 273:343–350

    Google Scholar 

  2. Ramis J, Mis R, Forn J, Torrent J, Gorina E, Jané F (1991) Pharmacokinetics of triflusal and its main metabolite HBT in healthy subjects following a single oral dose. Eur J Drug Metab Pharmacokinet 16:269–273

    Google Scholar 

  3. Ramis J, Torrent J, Mis R, Conte L, Barbanoj MJ, Jané J, Forn J (1990) Pharmacokinetics of triflusal after single and repeated doses in man. Int J Clin Pharmacol Ther Toxicol 28:350–354

    Google Scholar 

  4. De La Cruz JP, Mata JM, Sánchez de la Cuesta F (1992) Triflusal vs aspirin on the inhibition of human platelet and vascular cyclooxygenase. Gen Pharmacol 23:297–300

    Google Scholar 

  5. De La Cruz JP, Pavia J, Bellido I, González MC, Sánchez de la Cuesta (1988) Platelet antiaggregatory effect of triflusal in human whole blood. Methods Find Exp Clin Pharmacol 10:273–277

    Google Scholar 

  6. Castellarnau C, Sancho M, Vila L, Albors M, Rutllant M (1988) Effect and interaction studies of triflusal and other salicylic on cyclooxygenase in rats. Prostaglandins Leukot Essent Fatty Acids 31:83–89

    Google Scholar 

  7. Dejana E, Cerletti C, De Castellarnau C, Livio M, Galleti F, Latini R, De Gaetano G (1981) Salicylate-aspirin interaction in the rat. Evidence that salicylate accumulating during aspirin administration may protect vascular prostacyclin from aspirin induced inhibition. J Clin Invest 68:110–118

    Google Scholar 

  8. García-Rafanell J, Ramis J, Gomez L, Forn J (1986) Effect of triflusal and other salicylic acid derivatives on cyclic AMP levels in rat platelets. Arch Int Pharmacodyn Ther 284:155–165

    Google Scholar 

  9. De La Cruz JP, Pavia J, Bellido I, Sánchez de la Cuesta F (1988) Effect of triflusal and acetylsalicylic acid on platelet aggregation in human whole blood: influence of red blood cells and leukocytes. Methods Find Exp Clin Pharmacol 10:363–367

    Google Scholar 

  10. De La Cruz JP, Pavia J, Garcia-Arnes J, Sanchez de la Cuesta F (1988) Effects of triflusal and acetylsalicylic acid on platelet aggregation in whole blood from diabetic patients. Eur J Haematol 40:232–236

    Google Scholar 

  11. Esmatjes E, Maseras M, Gallego M, Coves MJ, Conget I (1989) Effect of treatment with an inhibitor of platelet aggregation on the evolution of background retinopathy: 2 years of follow-up. Diabetes Res Clin Pract 7:285–291

    Google Scholar 

  12. Guiteras P, Altimiras J, Aris A, et al (1989) Prevention of aortocoronary vein-graft attrition with low-dose aspirin and triflusal, both associated with dipyridamole: a randomized, double-blind, placebo-controlled trial. Eur Heart J 10:159–167

    Google Scholar 

  13. Cerletti C, Bonati M, Del Maschio A, Galletti F, Dejana E, Tognoni G, De Gaetano G (1984) Plasma levels of salicylate and aspirin in healthy volunteers: relevance to drug interaction on platelet function. J Lab Clin Med 103:869–877

    Google Scholar 

  14. Baumgartner HR, Handenschild C (1972) Adhesion of platelets to subendothelium. Ann NY Acad Sci 201:22–36

    Google Scholar 

  15. Baumgartner HR, Muggli R (1976) Adhesion and aggregation: morphological demonstration and quantitation in vivo and in vitro. In: Gordon JL (ed) Platelets in biology and pathology. North-Holland Biomedical Press, Cambridge, pp 23–59

    Google Scholar 

  16. Cardinal DC, Flower JR (1980) The electronic aggregometer: a novel device for assessing platelet behavior in blood. J Pharmacol Methods 3:135–158

    Google Scholar 

  17. Smith JB, Ingerman CM, Silver MJ (1976) Malondialdehyde formation as an indicator of prostaglandin production by human platelets. J Lab Clin Med 881:167–172

    Google Scholar 

  18. Sakariassen KS, Bolhuis PA, Sixma JJ (1980) Platelet adherence to subendothelium of human arteries in pulsatile and steady flow. Thromb Res 17:547–559

    Google Scholar 

  19. Baumgartner HR (1973) The role of blood flow in platelet adhesion, fibrin deposition and formation of mural thrombi. Microvasc Res 5:167–179

    Google Scholar 

  20. Baumgartner HR, Muggli R, Tschopp TB (1981) Antiplatelet drugs and the interaction between platelets, fibrin and components of vessel wall. In: Yoshida H, Hagihara Y, Ebashi S (eds) Clinical pharmacology. Teaching in pharmacology. Pergamon Press, Oxford, pp 21–29

    Google Scholar 

  21. Badimon L, Badimon JJ, Fuster V (1986) Platelet vessel wall interaction and von Willebrand disease. Evidence for the role of platelets in atherosclerosis. Biol Clin Hematol 8:37–41

    Google Scholar 

  22. Baumgartner HR (1979) Effects of acetylsalicylic acid, sulphinpirazone and dipyridamole on platelet adhesion and aggregation in flowing native and anticoagulated blood. Haemostasis 8:340–352

    Google Scholar 

  23. Escolar G, Bastida E, Castillo R, Ordinas A (1986) Development of a computer program to analyze the parameters of platelet-vessel wall interaction. Haemostasis 16:8–14

    Google Scholar 

  24. Escolar G, Bastida E, Ordinas A, Castillo R (1985) Interaction of platelets with subendothelium in humans treated with aspirin and dipyridamole. Thromb Res 40:419–424

    Google Scholar 

  25. Escolar G, Garrido M, Aznar-Salatti J, Ordinas A, Bastida E (1991) Comparison between human umbilical artery and rabbit abdominal aorta as substrate for platelet adhesion and platelet thrombus formation under flow conditions. Blood Vessels 28:520–531

    Google Scholar 

  26. Turitto VT, Baumgartner HR (1983) Platelet adhesion. In: Harker LA, Zimmerman TS, (eds) Measurements of platelet function. R, Edinburgh, pp 46–63

  27. De La Cruz JP, Bellido I, Camara S, Martos F, Sanchez de la Cuesta F (1986) Effects of acetylsalicylic acid on platelet aggregation in male and female whole blood: an in vitro study. Scand J Haematol 36:394–397

    Google Scholar 

  28. De La Cruz JP, Camara S, Bellido I, Carrasco T, Sanchez de la Cuesta F (1987) Platelet aggregation in human whole blood after chronic administration of aspirin. Thromb Res 46:133–140

    Google Scholar 

  29. Aguilar A, De La Cruz JP, Martos F, Garcia Arnes J, De Pablo J, Sanchez de la Cuesta F (1986) Efecto del dipiridamol (225 mg/día) y del ácido acetilsalicílico (150 mg/día) sobre algunos parámetros plaquetarios en la diabetes mellitus no complicada. Med Clin (Barc) 86:712–715

    Google Scholar 

  30. Weber E, Haas TA, Muller TH, Eisert WG, Hirsh J, Richardson M, Buchanan MR (1990) Relationship between vessel wall 13-HODE synthesis and vessel wall thrombogenecity following injury: influence of salicylate and dipyridamole treatment. Thromb Res 57:383–392

    Google Scholar 

  31. Aznar-Salatti J, Escolar G, Antón P, Bastida E, Ordinas A (1990) A rapid embedding procedure for the study of platelet interactions with extracellular matrices in a flowing system. Effect of aspirin on platelet activity. Methods Find Exp Clin Pharmacol 12:149–154

    Google Scholar 

  32. Ratnatunga CP, Edmondson SF, Rees GM, Kovacs IB (1992) High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation. Circulation 85:1077–1082

    Google Scholar 

  33. Siess W (1991) Multiple signal-transduction pathways synergize in platelet activation. NIPS 6:51–56

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

De La Cruz, J.P., García, P.J., Sánchez de la Cuesta, F. et al. Effects of triflusal and its main metabolite HTB on platelet interaction with subendothelium in healthy volunteers. Eur J Clin Pharmacol 47, 497–502 (1995). https://doi.org/10.1007/BF00193701

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00193701

Key words

Navigation