Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Acetylator phenotype and serum levels of sulfapyridine in patients with inflammatory bowel disease

  • 40 Accesses

  • 12 Citations

Summary

Twenty-eight outpatients receiving sulfasalazine for inflammatory bowel disease were monitored. Assessment of acetylator phenotype according to the percentage of acetylated sulfapyridine in serum provided a clear distinction between rapid and slow acetylators. In comparison, the percentage of acetylated sulfapyridine in saliva or urine was a less precise index of phenotype. Determination of saliva concentrations of sulfapyridine and N4-acetylsulfapyridine did not provide a reliable estimate of serum levels. Slow acetylators had significantly higher serum concentrations of sulfapyridine (21.9±14.0 [SD] µg/ml) than rapid acetylators (8.8±4.3 µg/ml) and had a higher incidence of toxicity (not statistically significant,p>0.05). Serum concentrations of sulfapyridine were significantly higher in patients with symptoms of toxicity (23.2±15.9 µg/ml) than those without (13.9±9.5 µg/ml) (p<0.05). However, serum concentrations of total sulfapyridine (sulfapyridine plus N4-acetylsulfapyridine) were not significantly different in patients with (32.9±21.2 µg/ml) or without (22.8±12.0 µg/ml) toxicity (p>0.05). For all patients serum concentrations of sulfapyridine (total sulfapyridine) ranged from 3.5 to 73.1 (5.7 to 95.1) µg/ml in patients with controlled disease and 6.3 to 38.0 (14.0 to 54.7) µg/ml in patients with active disease. A significant correlation between clinical status of disease and serum drug concentrations was only apparent for rapid acetylators (p<0.05). The daily sulfasalazine dosage (mg/kg of body weight, log value) and serum drug concentrations (log values) were highly correlated (p<0.05). For clinical evaluation of inflammatory bowel disease patients determination of serum sulfapyridine concentrations appears to be more important for monitoring toxicity than therapeutic efficacy of sulfasalazine. Assessment of acetylator status appears to be useful for predicting serum sulfapyridine levels in patients receiving sulfasalazine therapy.

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

References

  1. 1.

    Northfield TC (1979) Drug treatment of inflammatory bowel disease. Prescriber's J 19: 80–86

  2. 2.

    Poley JR (1978) Chronic inflammatory bowel disease in children and adolescents, Part I. South Med J 71: 935–948

  3. 3.

    Poley JR (1978) Chronic inflammatory bowel disease in children and adolescents. South Med J 71: 1123–1133

  4. 4.

    Khan AKA, Piris J, Truelove SC (1977) An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 2: 892–895

  5. 5.

    Serebro KS, Javett S, Abrahams C (1977) Sulphasalazine rectal enemas: Topical method of inducing remission of active ulcerative colitis affecting rectum and descending colon. Br Med J 4: 1264

  6. 6.

    van Hees PAM, Tuinte JHM, van Rossum JM van Tongeren JHM (1979) Influence of intestinal transit time on azo-reduction of salicylazosulphapyridine (salazopyrin). Gut 20: 300–304

  7. 7.

    Chapron DJ, Kramer PA, Mercik SA (1980) Kinetic discrimination of three sulfamethazine acetylation phenotypes. Clin Pharmacol Ther 27: 104–113

  8. 8.

    Das KM, Eastwood MA (1975) Acetylation polymorphism of sulfapyridine in patients with ulcerative colitis and Crohn's disease. Clin Pharmacol Ther 18: 514–520

  9. 9.

    Day JM, Houston JB (1980) Saliva: Plasma concentration relationships for sulphapyridine following sulphasalazine administration to normal volunteers and patients with inflammatory bowel disease. Br J Clin Pharmacol 9: 91–94

  10. 10.

    Fischer C, Klotz U (1979) High-performance liquid chromatographic determination of aminosalicylate, sulfapyridine and their metabolites. Its application to pharmacokinetic studies with salicylazosulfapyridine in man. J Chromatogr 162: 237–243

  11. 11.

    Das KM, Eastwood MA, McManus JPA, Sircus W (1973) The metabolism of salicylazosulfapyridine in ulcerative colitis. I. The relationship between metabolites and the response to treatment in inpatients. Gut 14: 631–636

  12. 12.

    Das KM, Eastwood MA, McManus JPA, Sircus W (1973) Adverse reactions during salicylazosulphayridine therapy and the relation with drug metabolism and acetylator phenotype. N Engl J Med 289: 491–495

  13. 13.

    Goodacre RL, Vanderlinden AB, Hamilton JP, Castelli M, Seaton T (1978) Hemolytic anemia in patients receiving sulfasalazine. Digestion 17: 503–508

  14. 14.

    Schroder H, Evans DAP (1972) Acetylator phenotype and adverse effects of sulphasalazine in healthy subjects. Gut 13: 278–284

  15. 15.

    Van Hees PAM, van Elferen LW, van Rossum JM, van Tongeren JH (1979) Hemolysis during salicylazosulfapyridine therapy. Am J Gastroenterol 70: 501–505

  16. 16.

    Das KM, Eastwood MA, McManus JPA, Sircus W (1973) The metabolism of salicylazosulfapyridine in ulcerative colitis. II. The relationship between metabolites and the progress of the disease studied in outpatients. Gut 14: 637–641

  17. 17.

    Sharp ME, Wallace SM, Hindmarsh KW, Brown MA (1980) HPLC and GLC analysis of sulfapyridine and acetylsulfapyridine: Development and selection of a suitable procedure for biological fluid analysis. Can J Pharm Sci 15: 35–38

  18. 18.

    Draper NP, Smith H (1976) Applied regression analysis. J Wiley and Sons, New York

  19. 19.

    Schroder H, Campbell DES (1972) Absorption, metabolism and excretion of salicylazosulfapyridine in man. Clin Pharmacol Ther 13: 539–551

  20. 20.

    Vree TB, O'Reilly WJ, Hekster VA, Damsma JE, van der Kleijn E (1980) Determination of the acetylator phenotype and pharmacokinetics of some sulphonamides in man. Clin Pharmacokinet 5: 274–294

  21. 21.

    duSouich P, McLean AJ, Stoeckel K, Ohlendorf D, Gibaldi M (1979) Screening methods using sulfamethazine for determining acetylator phenotype. Clin Pharmacol Ther 26: 757–765

  22. 22.

    Mucklow JC, Bending MR, Kahn GC, Dollery CT (1978) Drug concentration in saliva. Clin Pharmacol Ther 24: 563–570

  23. 23.

    Bates TR, Blumenthal HP, Peiniaszek HJ (1977) Salivary excretion and pharmacokinetics of sulfapyridine after sulfasalazine. Clin Pharmacol Ther 22: 917–927

  24. 24.

    Cowan GO, Das KM, Eastwood MA (1977) Further studies of sulphasalazine metabolism in the treatment of ulcerative colitis. Br Med J 2: 1057–1059

  25. 25.

    Goldstein PD, Alpers DH, Keating JP (1979) Sulfapyridine metabolites in children with inflammatory bowel disease receiving sulfasalazine. J Pediatr 95: 638–640

  26. 26.

    Singleton JW, Law DH, Kelly ML, Mekhjian HS, Sturdevant RAL (1979) National Cooperative Crohn's Disease Study: Adverse reactions to study drugs. Gastroenterology 77: 870–882

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Sharp, M.E., Wallace, S.M., Hindmarsh, K.W. et al. Acetylator phenotype and serum levels of sulfapyridine in patients with inflammatory bowel disease. Eur J Clin Pharmacol 21, 243–250 (1981). https://doi.org/10.1007/BF00627927

Download citation

Key words

  • sulfasalazine
  • sulfapyridine
  • acetylsulfapyridine
  • inflammatory bowel disease
  • toxicity
  • rapid acetylator
  • slow acetylator
  • acetylator phenotype