Skip to main content
Log in

Rapid recovery of in vivo prostacyclin formation after inhibition by aspirin

Evidence from measurements of the major urinary metabolite of prostacyclin by GC-MS

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

Summary

The effect of aspirin on the in vivo formation of prostacyclin and thromboxane A2 in normal healthy individuals was studied by measuring the urinary excretion of 2,3-dinor-6-keto-PGF and 2,3-dinor-TxB2 by gas chromatography-mass spectrometry. Administration of 500 mg aspirin twice daily caused a sustained reduction in the excretion of 2,3-dinor-TxB2 to 10–15% of the predose value, while the excretion of 2,3-dinor-6-keto-PGF was reduced for only about 3 hours after the aspirin dose. The data demonstrate a considerable difference in the inhibitory effect of aspirin on the in vivo synthesis of thromboxane A2 and prostacyclin.

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. Granström E, Diczfalusy U, Hamberg M (1983) The thromboxanes. In: Pace-Asciak C, Granström E (eds) Prostaglandins and related substances. Elsevier, Amsterdam, pp 45–94

    Google Scholar 

  2. Harker LA, Ritchie JL (1980) The role of platelets in acute vascular events. Circulation 62 [Suppl V]: 13–18

    Google Scholar 

  3. FitzGerald GA, Sherry S (1982) Pharmacology and pharmacokinetics of platelet-active drugs under current clinical investigation. In: Oates JA (ed) Prostaglandins and the cardiovascular system. Raven Press, NY, pp 107–172

    Google Scholar 

  4. Hamberg M, Svensson J, Samuelsson B (1975) Thromboxanes: A new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci USA 72: 2994–2998

    Google Scholar 

  5. Roth GJ, Majerus PW (1975) The mechanism of the effect of aspirin on human platelets. J Clin Invest 56: 624–632

    Google Scholar 

  6. Johnson RA, Morton DR, Kinner JH, Gorman RR, McGuire JC, Sun FF, Whittaker N, Bunting S, Salmon J, Moncada S, Vane JR (1976) The chemical structure of prostaglandin X (prostacyclin). Prostaglandins 12: 915–928

    Google Scholar 

  7. Frölich JC, Rosenkranz B (1984) Measurements of eicosanoids: Analysis of prostacyclin. Prostaglandins 27: 354–355

    Google Scholar 

  8. FitzGerald GA, Pedersen AK, Patrono C (1983) Analysis of prostacyclin and thromboxane biosynthesis in cardiovascular disease. Circulation 67: 1174–1177

    Google Scholar 

  9. Roberts LJ, Sweetman BJ, Oates JA (1981) Metabolism of thromboxane B2 in man. Identification of twenty urinary metabolites. J Biol Chem 256: 8384–8393

    Google Scholar 

  10. Rosenkranz B, Fischer C, Weimer KE, Frölich JC (1980) Metabolism of prostacyclin and 6-keto-prostaglandin F in man. J Biol Chem 21: 10194–10198

    Google Scholar 

  11. Vesterqvist O, Green K (1984) Urinary excretion of 2,3-dinorthromboxane B2 in man under normal conditions, following drugs and during some pathological conditions. Prostaglandins 27: 627–644

    Google Scholar 

  12. Vesterqvist O, Green K (1984) Development of a GC-MS method for quantitation of 2,3-dinor-6-keto-PGF and determination of the urinary excretion rates in healthy humans under normal conditions and following drugs. Prostaglandins 28: 139–154

    Google Scholar 

  13. Zipser RD, Smorlesi C (1984) Regulation of urinary thromboxane B2 in man: Influence of urinary flow rate and tubular transport. Prostaglandins 27: 257–271

    Google Scholar 

  14. Vesterqvist O, Green K, Lincoln FH, Sebek OK (1983) Development of a GC-MS method for quantitation of 2,3-dinor-TxB2 and determination of the daily urinary excretion rates in healthy humans. Thromb Res 33: 39–49

    Google Scholar 

  15. Rosenkranz B, Kitajima W, Frölich JC (1981) Relevance of urinary 6-keto-prostaglandin F determination. Kidney Int 19: 755–759

    Google Scholar 

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

    Google Scholar 

  17. Burch JW, Baenziger NL, Stanford N, Majerus PW (1978) Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin. Proc Natl Acad Sci USA 75: 5181–5184

    Google Scholar 

  18. Jaffe EA, Weksler BB (1979) Recovery of endothelial prostacyclin production after inhibition by low doses of aspirin. J Clin Invest 63: 532–535

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vesterqvist, O. Rapid recovery of in vivo prostacyclin formation after inhibition by aspirin. Eur J Clin Pharmacol 30, 69–73 (1986). https://doi.org/10.1007/BF00614198

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00614198

Key words

Navigation