European Journal of Clinical Pharmacology

, Volume 27, Issue 2, pp 165–168 | Cite as

Actions and interactions of acetylsalicylic acid, salicylic acid and diflunisal on platelet aggregation

  • E. Nitelius
  • B. Brantmark
  • B. Fredholm
  • U. Hedner
  • G. Plym Forshell
  • E. Wåhlin-Boll
  • A. Melander
Originals

Summary

Acetylsalicylic acid (ASA) is increasingly employed in the secondary prophylaxis of thromboembolic diseases, due to its capacity to inhibit platelet aggregation. The anti-aggregatory effect of ASA on platelets can be inhibited in vitro by a high concentration of salicylic acid (SA). SA is generated in vivo upon ASA administration, and the SA thus formed might impair the antiplatelet effect of ASA. To assess this possibility, the platelet response to ASA was tested in healthy volunteers before and after medication for 1 week with ASA 1 g t.i.d., with SA 1 g t.i.d., and with the SA derivative diflunisal 0.5 g b.i.d. Pre-medication test doses of 1 g ASA always inhibited platelet aggregation in vivo. Neither treatment with SA nor diflunisal, producing plasma steady-state concentrations of about 1.0 and 0.35 mmol/l, respectively, inhibited platelet aggregation. Nor did administration of SA, diflunisal or ASA itself impair the anti-aggregatory effect of a fresh test dose of ASA. ASA inhibited platelet aggregation in vitro at 0.03 mmol/l, whereas SA and diflunisal failed to impair platelet aggregation until concentrations exceeding 2.0 and 0.5 mmol/l, respectively, were reached. These findings make it unlikely that SA formed upon administration of ASA would impair the anti-aggregating capacity of ASA.

Key words

acetylsalicylic acid salicylic acid diflunisal platelet aggregation in vivo in vitro volunteers 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mustard JF, Kinlough-Rathbone RL, Packham MA (1980) Prostaglandins and platelets. Ann Rev Med 31: 89–96Google Scholar
  2. 2.
    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: 309–314Google Scholar
  3. 3.
    Vargaftig BB (1978) The inhibition of cyclo-oxygenase of rabbit platelets by aspirin is prevented by salicylic acid and by phenanthrolines. Eur J Pharmacol 50: 231–241Google Scholar
  4. 4.
    Brantmark B, Hedner U, Melander A, Wåhlin-Boll E (1981) Salicylate inhibition of antiplatelet effect of aspirin. Lancet 2: 1349Google Scholar
  5. 5.
    Born GVR (1962) Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 194: 927–929Google Scholar
  6. 6.
    Cronberg S, Caen JP (1979) Mg++-and Ca++-induced platelet aggregation and ADP. Thromb Diath Haemorrh 24: 432–437Google Scholar
  7. 7.
    Wåhlin-Boll E, Brantmark B, Hanson A, Melander A, Nilsson C (1981) High-pressure liquid chromatographic determination of acetylsalicylic acid, salicylic acid, diflunisal, indomethacin, indoprofen and indobufen. Eur J Clin Pharmacol 20: 375–378Google Scholar
  8. 8.
    Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nature (New Biol) 231: 232–235Google Scholar
  9. 9.
    Smith JB, Willis AL (1971) Aspirin selectively inhibits prostaglandin production in human platelets. Nature (New Biol) 231: 235–237Google Scholar
  10. 10.
    Roth GJ, Stanford N, Majerus PW (1975) Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci USA 72: 3073–3076Google Scholar
  11. 11.
    Preston FE, Whipps S, Jackson CA, French AJ, Wyld PJ, Stoddard CJ (1981) Inhibition of prostacyclin and platelet thromboxane A2 after low-dose aspirin. New Engl J Med 304: 76–79Google Scholar
  12. 12.
    Hanley SP, Bevan J, Cockbill SR, Heptinstall S (1981) Differential inhibition by low-dose aspirin of human venous prostacyclin synthesis and platelet thromboxane synthesis. Lancet 1: 969–971Google Scholar
  13. 13.
    Lewis Jr HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty III JE, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E, DeMots H (1983) Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 309: 396–403Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • E. Nitelius
    • 1
    • 2
    • 3
    • 4
  • B. Brantmark
    • 1
    • 2
    • 3
    • 4
  • B. Fredholm
    • 1
    • 2
    • 3
    • 4
  • U. Hedner
    • 1
    • 2
    • 3
    • 4
  • G. Plym Forshell
    • 1
    • 2
    • 3
    • 4
  • E. Wåhlin-Boll
    • 1
    • 2
    • 3
    • 4
  • A. Melander
    • 1
    • 2
    • 3
    • 4
    • 5
  1. 1.Department of Clinical Pharmacology and Coagulation DiseasesMalmö General HospitalMalmöSweden
  2. 2.Department of Clinical Pharmacology and Coagulation DiseasesUniversity of LundSweden
  3. 3.Department of MedicineHelsingborg HospitalHelsingborgSweden
  4. 4.Research DepartmentAB LeoHelsingborgSweden
  5. 5.Division of Clinical PharmacologyLund University Health Sciences CentreDalbySweden

Personalised recommendations