Advertisement

European Journal of Clinical Pharmacology

, Volume 32, Issue 2, pp 153–158 | Cite as

Salicyl phenolic glucuronide pharmacokinetics in patients with rheumatoid arthritis

  • F. Bochner
  • G. G. Graham
  • A. Polverino
  • D. M. Imhoff
  • R. A. Tregenza
  • P. E. Rolan
  • L. G. Cleland
Originals

Summary

The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8±0.3, 1.7±0.2, and 1.5±0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2±1.1 to 7.1±1.1 to 10.5±1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect of the plasma concentration of unbound SA (13.4±1.6, 11.0±1.4, and 6.6±1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies.

Key words

salicyl phenolic glucuronide rheumatoid arthritis aspirin pharmacokinetics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bedford C, Cummings AJ, Martin BK (1965) A kinetic study of the elimination of salicylate in man. Br J Pharmacol 24: 418–431Google Scholar
  2. 2.
    Bochner F, Graham GG, Cham BE, Imhoff DM, Haavisto TM (1981) Salicylate metabolite kinetics after several salicylates. Clin Pharmacol Ther 30: 266–275Google Scholar
  3. 3.
    Levy G, Amsel LP, Elliott HC (1969) Kinetics of salicyluric acid elimination in man. J Pharm Sci 58: 827–829Google Scholar
  4. 4.
    Levy G, Tsuchiya T, Amsel LP (1972) Limited capacity for salicyl phenolic glucuronide formation and its effect on the kinetics of salicylate elimination in man. Clin Pharmacol Ther 13: 258–268Google Scholar
  5. 5.
    Furst DE, Gupta N, Paulus HE (1977) Salicylate metabolism in twins. Evidence suggesting a genetic influence and induction of salicylurate formation. J Clin Invest 60: 32–42Google Scholar
  6. 6.
    Günsberg M, Bochner F, Graham G, Imhoff D, Parsons G, Cham B (1984) Disposition of and clinical response to salicylates in patients with rheumatoid disease. Clin Pharmacol Ther 35: 585–593Google Scholar
  7. 7.
    Tsuchiya T, Levy G (1972) Biotransformation of salicylic acid to its acyl and phenolic glucuronides in man. J Pharm Sci 61: 800–801Google Scholar
  8. 8.
    Day RO, Furst DE, Dromgoole SH, Paulus HE (1982) Decline in steady-state serum salicylic acid concentrations with time in normal volunteers given high dose aspirin. Aust NZ J Med 12: 557–558Google Scholar
  9. 9.
    Borgä O, Odar-Cederlöf I, Ringberger V-A, Norlin A (1976) Protein binding of salicylate in uremic and normal plasma. Clin Pharmacol Ther 20: 464–475Google Scholar
  10. 10.
    Ekstrand R, Alvan G, Borgä O (1979) Concentration dependent plasma protein binding of salicylate in rheumatoid patients. Clin Pharmacokinet 4: 137–143Google Scholar
  11. 11.
    Furst DE, Tozer TN, Melmon KL (1979) Salicylate clearance, the resultant of protein binding and metabolism. Clin Pharmacol Ther 26: 380–389Google Scholar
  12. 12.
    Wosilait WD (1976) Theoretical analysis of the binding of salicylate by human serum albumin: The relationship between free and bound drug and therapeutic levels. Eur J Clin Pharmacol 9: 285–290Google Scholar
  13. 13.
    Smith PK, Gleason HL, Stoll CG, Ogorzalek S (1946) Studies on the pharmacology of salicylates. J Pharmacol Exp Ther 87: 237–255Google Scholar
  14. 14.
    Imhoff DM, Reece PA, Dimitriades E, Ward AD, Bochner F (1986) Direct measurement of salicyl phenolic glucuronide in human urine. Ther Drug Monit 8: 321–325Google Scholar
  15. 15.
    Ropes MW, Bennett GA, Lobb S, Jacox R, Jessar RA (1959) Diagnostic criteria for rheumatoid arthritis. Ann Rheum Dis 18: 49–53Google Scholar
  16. 16.
    Ritchie DM, Boyle JA, McInnes JM, Jasani MK, Dalakos TG, Grieveson P, Buchanan WW (1968) Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Quart J Med 147: 393–406Google Scholar
  17. 17.
    Cham BE, Johns D, Bochner F, Imhoff DM, Rowland M (1979) Simultaneous liquid-chromatographic quantitation of salicylic acid, salicyluric acid, and gentisic acid in plasma. Clin Chem 25: 1420–1425Google Scholar
  18. 18.
    Wilkinson GR, Shand DG (1975) Physiological approach to hepatic drug clearance. Clin Pharmacol Ther 18: 377–390Google Scholar
  19. 19.
    Rowland M, Riegelman S (1968) Pharmacokinetics of acetylsalicylic acid and salicylic acid after intravenous administration in man. J Pharm Sci 57: 1313–1319Google Scholar
  20. 20.
    Levy G, Tsuchiya T (1972) Salicylate accumulation kinetics in man. N Engl J Med 287: 430–432Google Scholar
  21. 21.
    Portek I, Graham GG, Fleming A (1981) Enteric coated pelletized aspirin: gastrointestinal blood loss and bioavailability. Med J Aust 2: 39–40Google Scholar
  22. 22.
    Markiewicz A, Semenowicz K (1979) Time dependent changes in the pharmacokinetics of aspirin. Int J Clin Pharmacol Biopharm 17: 409–411Google Scholar
  23. 23.
    Mandelli M, Tognoni G (1980) Monitoring plasma concentrations of salicylate. Clin Pharmacokinet 5: 424–440Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • F. Bochner
    • 1
  • G. G. Graham
    • 2
  • A. Polverino
    • 1
  • D. M. Imhoff
    • 1
  • R. A. Tregenza
    • 3
  • P. E. Rolan
    • 1
  • L. G. Cleland
    • 3
  1. 1.Department of Clinical and Experimental PharmacologyUniversity of Adelaide and Royal Adelaide Hospital
  2. 2.School of Physiology and PharmacologyUniversity of New South WalesSydney
  3. 3.Departments of Physiotherapy and RheumatologyRoyal Adelaide Hospital

Personalised recommendations