Skip to main content
SpringerLink
Log in

Plasma drug and antiplatelet profiles of the original acetylsalicylic acid preparations used in the AMIS, PARIS and German-Austrian trials for secondary prevention of myocardial infarction

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

Summary

In a cross-over study 6 healthy male subjects were given for 9 days the acetylsalicylic acid (ASA) preparations used in the Aspirin Myocardial Infarction Study (AMIS), Persantine-Aspirin Reinfarction Study (PARIS) and German-Austrian secondary heart attack prevention trials, exactly according to the original study protocols. Plasma concentrations of ASA and its main metabolites salicylic acid (SA) and salicyluric acid (SUA), as well as platelet function (collagen-induced platelet aggregation; tissue extract-induced change in platelet shape) were studied repeatedly on the first day of each medication period and were again examined on the sixth and ninth days. Differences in the plasma concentrations of ASA and its metabolites were found only on the first day, probably as a result of different absorption rates. Collagen-induced platelet aggregation was more rapidly inhibited the faster the preparation was absorbed. Each ASA preparation inhibited tissue extract-induced platelet shape change from the first dose, although statistically significant inhibition was seen only with the AMIS preparation. It is concluded that differences in the antithrombotic efficiency of ASA cannot be explained by differences in the pharmacokinetic and antiplatelet profiles of the various ASA preparations tested.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ali M, McDonald JW, Thiessen JJ, Coates PE (1980) Plasma acetylsalicylate and salicylate and platelet cyclooxygenase activity following plain and enteric-coated aspirin. Stroke 11: 9–13

    Google Scholar 

  2. Aspirin Myocardial Infarction Study Research Group (1980) A randomized controlled trial of aspirin in persons recovered from myocardial infarction. J Am Med Assoc 243: 661–669

    Google Scholar 

  3. Bender N, Kirchmaier CM, Bartsch B, Lindenborn D, Breddin HK (1979) Stimulation of blood platelets by extracts of subcutaneous tissue. Thromb Res 14: 341–351

    Google Scholar 

  4. Bochner F, Ehns MJ, Ross-Lee CM, Cham B, Bunce IH (1980) The relative bioavailability of acetylsalicylic acid from a soluble and an enteric-coated preparation and the effect of each on platelet function. Clin Exp Pharmacol 8: 649–650

    Google Scholar 

  5. Brantmark B, Wåhlin-Boll E, Melander A (1982) Bioavailability of acetylsalicylic acid and salicylic acid from rapid-and slow-release formulations and in combination with dipyridamole. Eur J Clin Pharmacol 22: 309–314

    Google Scholar 

  6. Breddin HK (1968) Experimental and clinical investigations on the adhesion and aggregation of human platelets. Exp Biol Med 3: 14–23

    Google Scholar 

  7. Breddin HK, Loew D, Lechner K, Überla K, Walters E (1980) Secondary prevention of myocardial infarction. A comparison of acetylsalicylic acid, placebo and phenprocoumon. Haemostasis 9: 325–344

    Google Scholar 

  8. Breddin HK (1981) Zum Wirkungsmechanismus und zur Dosierung thrombozytenfunktionshemmender Medikamente. In: Breddin K, Loew D, Überla K, Dorndorf W, Marx (eds) Prophylaxe venöser, peripherer, kardialer und zerebraler Gefäßkrankheiten mit Acetylsalicylsäure. FK Schattauer, Stuttgart New York, pp 9–22

    Google Scholar 

  9. Breddin HK, Bender N, Kirchmaier CM (1984) On the mechanism of platelet activation during hemostasis and thrombosis and on the effect of platelet inhibition drugs. In: Strano A (ed) Thrombosis and cardiovascular diseases. Plenum Publishers New York, pp 145–154

    Google Scholar 

  10. Buchanan MR, Rischke JA, Hirsh J (1982) Aspirin inhibits platelet function independent of the acetylation of the cyclooxygenase. Thromb Res 25: 363–373

    Google Scholar 

  11. Buchanan MR, Rischke JR, Butt R, Turpie AGG, Hirsh J, Rosenfeld J (1983) The sex-related differences in aspirin pharmacokinetics in rabbits and man and its relationship to antiplatelet effects. Thromb Res 29: 125–139

    Google Scholar 

  12. Burch JW, Stanford N, Majerus P (1978) Inhibition of platelet synthetase by oral aspirin. J Clin Invest 61: 314–319

    Google Scholar 

  13. Canadian Cooperative Study Group (1980) Randomized trial of therapy with platelet antiaggregants for threatend stroke. Can Med Assoc J 122: 293–296

    Google Scholar 

  14. Chesebro JH, Clements IP, Fuster K, Elveback LR, Smith HC, Bardsley WT, Frye RL, Hohnes DR, Vlietstra RE, Phith JR, Wallace RB, Puga FJ, Orszulak TA, Piehler JM, Schaff HV, Danielson GK (1982) A platelet inhibitor drug trial in coronary artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency. N Engl J Med 307: 73–80

    Google Scholar 

  15. Chesebro JH, Fuster V, Elveback LR, Clements IP, Smith HC, Hohnes DR, Bardsley WT, Pluth JR, Wallace RB, Puga FJ, Orszulak TA, Piehler JM, Danielson GK, Schaff HV, Frye RL (1984) Effect of dipyridamole and aspirin on lat vein-graft patency after coronary bypass operation. N Engl J Med 310: 209–314

    Google Scholar 

  16. De Caterina RD, Gianessi D, Bernini W, Boem A, Michelassi C, Patrignani P, Patrono C (1985) Equal antiplatelet effects of 50 and 324 mg aspirin daily in patients with myocardial infarction. Thromb Haemostas 54: 240

    Google Scholar 

  17. Ellis EF, Wright KF, Jones PS, Richardson PW, Ellis CK (1980) Effect of oral aspirin dose on platelet aggregation and vascular prostacyclin (PGI2) synthesis in human and rabbits. J Cardiovasc Pharmacol 2: 387–397

    Google Scholar 

  18. Fields WS, Lemak NA, Frankowski RF, Hardy RJ (1977) Controlled trial of aspirin in cerebral ischemia. Stroke 8: 301–316

    Google Scholar 

  19. Harris WH, Salzmann EW, Athanasoulis CA, Waltman AC, DeSanctis RS (1977) Aspirin prophylaxis of venous thromboembolism after total hip replacement. N Engl J Med 297: 1246–1249

    Google Scholar 

  20. Kelton JG (1983) Antiplatelet agents: Rationale and results. Clin Haematol 12: 311–354

    Google Scholar 

  21. Kelton JG, Carter CJ, Rosenfeld J, Nguyeu KB (1984) A study of the bioavailability and platelet inhibitory effects of a new enteric-coated acetylsalicylic acid preparation. Thromb Res 34: 561–566

    Google Scholar 

  22. Kirchmaier CM, Bender N, Wilhelm B, Al-Sayegh A, Breddin HK (1979) A hemostasis-activating factor (HAF) in subcutaneous tissue-extracts: effects on morphological platelet changes. Thromb Res 16: 81–91

    Google Scholar 

  23. Lorenz RL, Weber M, Kotzür J, Thiesen K, Schacky CV, Meister W, Reichardt B, Weber PC (1984) Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily). Lancet 1: 1261–1264

    Google Scholar 

  24. Marcus AJ (1983a) Aspirin as an antithrombotic medication. N Engl J Med 309: 1515–1517

    Google Scholar 

  25. Marcus AJ (1983b) Recent progress in the role of platelets in occlusive vascular disease. Stroke 14: 475–479

    Google Scholar 

  26. Numano RM, Yajima M, Numano FE, Shimokado K, Nomora S, Maruyama Y (1985) Low dose of aspirin treatment for cardiovascular disease. Thromb Haemost 54: 66

    Google Scholar 

  27. Nuotto E, Gordin A, Paasonen MK, Metsä-Ketelä T, Lamminsiva U (1983) Effect of acetylsalicylic acid on plasma thromboxane B2 and platelet aggregation in man. Eur J Clin Pharmacol 25: 313–317

    Google Scholar 

  28. O'Grady J, Moncada S (1978) Aspirin: A paradoxical effect on bleeding time. Lancet 2: 780

    Google Scholar 

  29. Patrignani P, Filabozzi P, Patrono C (1982) Selective cumulative inhibition of platelet thromboxane production by low dose aspirin in healthy subjects. J Clin Invest 69: 1366–1372

    Google Scholar 

  30. Patrono C, Ciabattoni G, Pinca E, Pugliese F, Castrucci G, DeSalvo A, Satta MA, Peskar BA (1980) Low-dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res 17: 317–327

    Google Scholar 

  31. Persantine-Aspirin Reinfarction Study Research Group (1980) Persantine and aspirin in coronary heart disease. Circulation 62: 449–461

    Google Scholar 

  32. Pietsch U, Lippmann M, Scharrer I, Breddin HK (1977) Neue Befunde zur Wirkung der Acetylsalicylsäure: Die Hemmwirkung auf den Formwandel der Thrombozyten und ihre Bedeutung für die Dosierung als Antithrombotikum. In: Alexander K, Cachovan K (eds) Diabetische Angiopathien. Gerhard Witzstrock, Baden-Baden, pp 348–351

    Google Scholar 

  33. Rehders K, Simrock R, Spahn H, Mutschler E, Breddin HK (1985) Plasma salicylate levels and platelet function after acute and chronic administration of slow-release acetylsalicylic acid (Monobeltin). Eur J Clin Pharmacol 27: 683–687

    Google Scholar 

  34. Roth GJ, Stanford N, Majerus PW (1975) Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci USA 72: 3073–3076

    Google Scholar 

  35. Siebert DJ, Bochner F, Imhoff DM, Watts S, Lloyd JV, Field J, Gabb BW (1983) Aspirin kinetics and platelet aggregation in man. Clin Pharmacol Ther 33: 367–374

    Google Scholar 

  36. Spahn H, Mutschler E (1983) Die dünnschichtchromatographische Bestimmung von Acetylsalicylsäure, Salicylsäure und Salicylursäure im Plasma durch Fluoreszenzmessung. Arch Pharm 316: 364–367

    Google Scholar 

  37. Toivanen J, Ylikorkala O, Viinikka L (1984) One milligramme of acetylsalicylic acid daily inhibits platelet thromboxane A2 synthesis. Thromb Res 35: 681–687

    Google Scholar 

  38. Weksler BB, Pett SB, Alonso D, Richter RC, Stelzer P, Subramanian V, Tack-Goldman K, Gay WA (1983) Differential inhibition by aspirin of vascular and platelet prostaglandin synthesis in atherosclerotic patients. New Engl J Med 308: 800–805

    Google Scholar 

  39. Weksler BB, Kent JL, Rudolph D, Scherer PB, Levy DE (1985) Effects of low dose aspirin on platelet function in patients with recent cerebral ischemia. Stroke 16: 5–9

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Angiology, J.W.Goethe University, Frankfurt/Main, Federal Republic of Germany

    R. Simrock, K. Rehders & H. K. Breddin

  2. Department of Pharmacology, Faculty of Pharmacy and Biochemistry, J.W.Goethe University, Frankfurt/Main, Federal Republic of Germany

    H. Spahn & E. Mutschler

Authors
  1. R. Simrock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Rehders
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Spahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Mutschler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. K. Breddin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Simrock, R., Rehders, K., Spahn, H. et al. Plasma drug and antiplatelet profiles of the original acetylsalicylic acid preparations used in the AMIS, PARIS and German-Austrian trials for secondary prevention of myocardial infarction. Eur J Clin Pharmacol 33, 541–547 (1988). https://doi.org/10.1007/BF00542484

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00542484

Key words

Search

Navigation