The systemic load and efficient delivery of active 5-aminosalicyclic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine

Background: There have been reports of nephrotoxic reactions in patients wi th ulcerative colitis treated with 5-aminosalicyclic acid (5-ASA) preparati ons. Aim: To compare the efficacy in delivery of active 5-ASA to the colon and t he systemic load as the basis for potential long-term toxicity during treat ment with olsalazine or mesalazine in patients with ulcerative colitis in r emission. Patients and Methods: Fifteen patients with ulcerative colitis were treated with obalazine or mesalazine, each for 7 days in an open, randomized, cros sover design study. 5-ASA and acetyl-5-ASA (Ac-5-ASA) in plasma and urine w ere measured by high performance liquid chromatography. Results: The plasma concentration of 5-ASA was 1.2 +/- 0.1 mu mol/L (mean /- S.E.M.) for olsalazine and 8.0 +/- 1.9 mu moI/L for mesalazine, while th e plasma concentration of Ac-5-ASA was 2.8 +/- 0.2 mu mol/L for olsalazine and 10.8 +/- 1.6 mu mol/L for mesalazine. The amount of 5-ASA excreted in t he urine was 68 +/- 30 mu mol/24 h for olsalazine and 593 +/- 164 mu mol/24 h for mesalazine, The amount of Ac-5-ASA in the urine was 1260 +/- 102 mu mol/24 h for olsalazine and 3223 +/- 229 mu mol/24 h for mesalazine. The ur inary recovery of total 5-ASA plus Ac-5-ASA (as a percentage of the given d ose) was 23 +/- 2.1% for olsalazine and 39 +/- 3.6% for mesalazine. The rat io 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 A c-5-ASA (1.7). Moreover, in the mesalazine group there was a large variatio n in the individual plasma concentrations of 5-ASA and Ac-5-ASA, with maxim al values 5-6-fold higher than that in the olsalazine group. Conclusion: The systemic load of active 5-ASA is significantly higher for m esalazine than for olsalazine, when based on the dosages given and when cal culated 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 hare long-term safety implications.