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Sulfapyridine metabolites in children with inflammatory bowel disease receiving sulfasalazine
Insights
Sulfasalazine (SASP) is safe for children with inflammatory colon disease, with doses of 1.5 to 2.0 gm/m2 achieving therapeutic serum sulfapyridine (SP) levels. Routine SP monitoring is not necessary for effective treatment.
Area of Science:
- Pediatric Gastroenterology
- Pharmacology
- Inflammatory Bowel Disease
Background:
- Chronic inflammatory conditions of the colon in children require effective treatment.
- Sulfasalazine (SASP) is a common therapeutic agent, but optimal dosing and serum level correlations in pediatric patients require further investigation.
Purpose of the Study:
- To evaluate the safety and efficacy of sulfasalazine (SASP) in pediatric patients with chronic inflammatory colon disease.
- To determine the correlation between SASP dosage, serum sulfapyridine (SP) levels, and patient metabolic profiles (acetylation and hydroxylation).
Main Methods:
- Fifteen pediatric outpatients with chronic inflammatory colon disease received SASP at varying doses (1-4 gm/day).
- Serum sulfapyridine (SP) levels were measured and correlated with administered dose (gm/m2), disease activity, and patient acetylation/hydroxylation status.
Main Results:
- A SASP dose of 1.5 to 2.0 gm/m2 was safely administered and typically achieved therapeutic serum SP levels (≥17 µg/ml).
- Patients with slow acetylation or hydroxylation exhibited significantly higher SP levels compared to rapid metabolizers.
- No correlation was found between SP levels and disease activity, and no toxic SP levels (>50 µg/ml) were observed.
Conclusions:
- Sulfasalazine (SASP) dosing between 1.5 and 2.0 gm/m2 is safe and effective for children with inflammatory colon disease, achieving therapeutic serum sulfapyridine (SP) levels.
- Individual variations in SP levels due to acetylation and hydroxylation rates do not necessitate routine therapeutic drug monitoring of SP levels for SASP therapy in children.
Abstract:
Fifteen children followed as outpatients with chronic inflammatory disease of the colon were given sulfasalazine in doses from 1 to 4 gm/day (22 to 68 mg/kg, or 0.69 to 2.33 gm/m2). No correlation was found between the dose/m2 administered and the total serum sulfapyridine levels. However, 11 of 15 patients achieved SP levels greater than or equal to 17 micrograms/ml, a level approximating that reputedly associated with therapeutic efficacy. Patients who were either slow acetylators or slow hydroxylators of sulfapyridine had total SP levels significantly higher than patients who were both rapid acetylators and hydroxylators (20.0 +/- 1.2 vs 14.6 +/- 1.6). Total SP serum levels were not correlated with the activity of the disease. No toxic levels (greater than 50 micrograms/ml of SP) were encountered. We conclude that a dose of SASP in the range of 1.5 to 2.0 gm/m2 can be safely administered to children and is usually associated with serum SP levels considered in the therapeutic range. Although one-third of children are both rapid acetylators and hydroxylators and will have somewhat lower SP levels, the routine monitoring of SASP therapy with SP levels is not necessary for management of disease.