Steady-State Kinetics of 5-Aminosalicylic Acid and Sulfapyridine during Sulfasalazine Prophylaxis in Ulcerative Colitis

Abstract

Fifteen adult and 19 pediatric outpatients with ulcerative colitis were studied to determine the steady-state kinetics of 5-aminosalicylic acid (5-ASA) released from salazosulfapyridine (SASP). Results of excretion in adults (mean 24-h recovery of 5-ASA, 21% in urine and 57% in feces) were compatible with those of healthy volunteers. Since mean SASP dose/kg body weight (about 50 mg/kg) and compliance (reflected in sulfapyridine recovery) were equal in adults and pediatric patients, the results of the patient groups could be compared. Near-complete azo reduction of SASP occurs in children. Absorption and excretion of 5-ASA and metabolism to acetyl-5-ASA did not differ statistically between pediatric and adult patients. However, the fecal excretion of the drug and its metabolites was significantly lower in young patients, although fecal concentrations were the same. The present results demonstrate that SASP is an excellent sustained-release drug for the delivery of 5-ASA to the lower part of the bowel system and provide a reference for comparison of 5-ASA kinetics after treatment with newer 5-ASA preparations.

Effect of 5-Aminosalicylic Acid and Analogous Substances on Superoxide Generation and Intracellular Free Calcium in Human Neutrophilic Granulocytes

“…Using a zymosan-stimulated PMNs system for superoxide production, Miyachi et al (14) did not find any effect of 5-ASA. However, in their assay 5-ASA was tested up to a concentration of 0.065 mM, which is approximately 30 times below the pharmacologically relevant concentration, as the concentration of 5-ASA in the colon during conventional SAZ treatment is more than 2 mM (35).…”

Tests of renal function in patients with quiescent colitis: effects of drug treatment.

“…al-microglobulin concentrations were measured by enzyme immunoassay using an identical methodology to that described for transferrin. '5 The range of the assay was 0.1 to 10.0 mg/l and within and between batch coefficients of variation were 2.4% and 4 …”

“…2 The effect of mesalazine treatment on renal function has been a particular concern as mesalazine has structural similarities to aspirin and phenacetin, both of which have been implicated in analgesic nephropathy.3 Chronic sulphasalazine treatment does not seem to be nephrotoxic but the systemic absorption of 5-ASA from sulphasalazine is relatively low. 4 Delayed release mesalazine formulations release their contents rapidly in the distal small intestine and proximal colon. Plasma concentrations of 5-ASA may therefore be higher in patients taking delayed release mesalazine than in patients taking equivalent doses of sulphasalazine.'…”

The antiinflammatory moiety of sulfasalazine, 5-aminosalicylic acid, is a radical scavenger

“…certain resinous extracts from plants, such as nordihydroguaiaretic acid and flavonoids), and some arylamines used in industrial production to prevent autooxidation [4,5]. 5-ASA is present in millimolar concentrations in the large bowel of patients treated with sulfasalazinc [7]. Various mechanisms, including inter-ference with arachidonic acid metabolism, have been proposed to explain the antiinflammatory activity of 5-ASA released locally in the colon from sulfasalazine, but none seem to provide the full explanation [8].…”