Clinical Pharmacokinetics

, Volume 1, Issue 6, pp 406–425 | Cite as

Clinical Pharmacokinetics of Sulphasalazine

  • Kiron M. Das
  • R. Dubin
Article

Summary

Sulphasalazine consists of 5-aminosalicylic acid and sulphapyridine both linked together by an azo bond. Sulphasalazine is clearly useful in long-term management of ulcerative colitis and may be useful in Crohn’s disease. The absorption, metabolism and excretion of sulphasalazine is similar in volunteers and patients with ulcerative colitis or Crohn’s disease. Sulphasalazine serves as a vehicle to deliver its possible active components, 5-aminosalicylic acid and sulphapyridine, to the colon in higher concentrations than could be achieved by oral administration of either one alone. Sulphasalazine reaches the colon mostly unchanged and is split by gut bacteria at the azo linkage, releasing 5-aminosalicylic acid and sulphapyridine.

5-Aminosalicylic acid may act locally and is not absorbed to any great extent. On the contrary, sulphapyridine is mostly absorbed from the colon and may act both locally, during mucosal absorption, and systemically. A positive correlation exists between serum total sulphapyridine concentration and both therapeutic efficacy and toxicity. Sulphapyridine metabolism is largely determined by inherited acetylator phenotype, either slow or fast. Slow acetylators have higher levels of free sulphapyridine and lower levels of acetylated sulphapyridine than fast acetylators, and are likely to have more toxic symptoms on equivalent doses of sulphasalazine. Therapeutic effects of sulphasalazine in ulcerative colitis and Crohn’s disease correlate with serum concentrations of total sulphapyridine (20 to 50μg/ml), and toxicity with total sulphapyridine concentrations > 50μg/ml. Side-effects are mostly observed among slow acetylators. In long-term therapy of ulcerative colitis doses of 2 to 3g/day of sulphasalazine are most likely to sustain remissions and avoid toxicity. During therapy with sulphasalazine, determination of acetylator phenotype and total sulphapyridine concentration can guide effective dosage and avoid side-effects. A single serum sample for free and acetylated sulphapyridine concentrations is sufficient for this purpose.

Keywords

Ulcerative Colitis Clinical Pharmacokinetic Sulphasalazine Slow Acetylators Acetylator Phenotype 

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© ADIS Press 1976

Authors and Affiliations

  • Kiron M. Das
    • 1
  • R. Dubin
    • 1
  1. 1.Department of Medicine, Gastrointestinal and Liver Disease DivisionAlbert Einstein College of MedicineNew YorkUSA

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