The systemic load and efficient delivery of active 5-aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine.
BACKGROUND
There have been reports of nephrotoxic reactions in patients with ulcerative colitis treated with 5-aminosalicylic acid (5-ASA) preparations.


OBJECTIVE
To compare the efficacy in delivery of active 5-ASA to the colon and the systemic load as the basis for potential long-term toxicity during treatment with olsalazine or mesalazine in patients with ulcerative colitis in remission.


METHODS
Fifteen patients with ulcerative colitis were treated with olsalazine or mesalazine, each for 7 days in an open, randomized, crossover design study. 5-ASA and acetyl-5-ASA (Ac-5-ASA) in plasma and urine were measured by high performance liquid chromatography.


RESULTS
The plasma concentration of 5-ASA was 1.2 +/- 0.1 micromol/L (mean +/- S.E.M.) for olsalazine and 8.0 +/- 1.9 micromol/L for mesalazine, while the plasma concentration of Ac-5-ASA was 2.8 +/- 0.2 micromol/L for olsalazine and 10.8 +/- 1.6 micromol/L for mesalazine. The amount of 5-ASA excreted in the urine was 68 +/- 30 micromol/24 h for olsalazine and 593 +/- 164 micromol/24 h for mesalazine. The amount of Ac-5-ASA in the urine was 1260 +/- 102 micromol/24 h for olsalazine and 3223 +/- 229 micromol/24 h for mesalazine. The urinary recovery of total 5-ASA plus Ac-5-ASA (as a percentage of the given dose) was 23 +/- 2.1% for olsalazine and 39 +/- 3.6% for mesalazine. The ratio between the plasma concentrations of mesalazine and olsalazine differed significantly both for 5-ASA (5.1) and Ac-5-ASA (3.6); for 5-ASA (9. 9) and Ac-5-ASA (2.6) in urine, and for the urinary recovery of total 5-ASA plus Ac-5-ASA (1.7). Moreover, in the mesalazine group there was a large variation in the individual plasma concentrations of 5-ASA and Ac-5-ASA, with maximal values 5-6-fold higher than that in the olsalazine group.


CONCLUSIONS
The systemic load of active 5-ASA is significantly higher for mesalazine than for olsalazine, when based on the dosages given and when calculated on an equimolar basis. Some of the patients in the mesalazine group showed unexpected high levels of plasma and urinary 5-ASA concentrations, a finding which may have long-term safety implications.
Støa-Birketvedt
G
G
Laboratory of Gastroenterology, Institute of Clinical Medicine, University of Tromso, Tromso, Norway. gsb42nor@aol.com
Florholmen
J
J
D000328:Adult; D000368:Aged; D000636:Aminosalicylic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001241:Aspirin / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003106:Colon / Q000378:metabolism; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008875:Middle Aged
D000636:Aminosalicylic Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine; D001241:Aspirin; C032587:olsalazine