ISSN:
1365-2036
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background: All 5-aminosalicylic acid (5-ASA) preparations are potentially nephrotoxic, but there has been concern that newer delivery systems may increase this risk, either because of altered absorption or altered metabolism. Previous studies of 5-ASA absorption and excretion have usually either been performed in healthy controls or have only examined short-term therapy. 5-ASA and N-acetyl-5-ASA have therefore been measured in blood samples, and N-acetyl-5-ASA in urine samples, from patients with ulcerative colitis on long-term maintenance with different 5-ASA preparations and compared with sensitive markers of renal damage. Methods: Patients receiving mesalazine (Asacol) (n=13), sulphasalazine (n=12) or olsalazine (Dipentum) (n=8), all at doses within the recommended range were studied. Six-hour and trough serum concentrations of 5-ASA and N-acetyl-5-ASA and 24-h urinary excretion of N-acetyl-5-ASA were measured by high-performance liquid chromatography. Results: Absorption of 5-ASA, assessed as 24-h excretion of N-acetyl-5-ASA expressed as molar % of ingested dose, was greater in patients receiving mesalazine, 23.25±10.65% (mean±s.d.; n=13), than those receiving sulphasalazine (11.16±10.52%, n=12; P=0.003) or olsalazine (9.70±3.89%, n=8; P〈0.002). The ratio of 5-ASA:N-acetyl-5-ASA in the serum 6 h after dose was also greater with mesalazine (1.02±0.44, mean±s.d.) than sulphasalazine (0.54±0.44, P〈0.02) or olsalazine (0.38±0.44, P〈0.005). Urinary markers of tubular damage were increased in four of 33 patients, but showed no correlation with concentration of 5-ASA or N-acetyl-5-ASA in serum and N-acetyl-5-ASA in urine, nor with lifetime dose or average daily dose of 5-ASA. Conclusions: In patients with ulcerative colitis receiving maintenance 5-ASA therapy there was greater absorption and less acetylation of 5-ASA from mesalazine (Asacol) compared with sulphasalazine or olsalazine, but no evidence from this study that this resulted in increased nephrotoxicity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1365-2036.1996.85257000.x
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