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The pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro‐drugs used in the management of ulcerative colitis
Author(s) -
Sandborn W. J.,
Hanauer S. B.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2003.01408.x
Subject(s) - mesalazine , sulfasalazine , medicine , ulcerative colitis , pharmacokinetics , gastroenterology , excretion , cmax , urine , disease
Summary Aim : To quantify through systematic review the pharmacokinetic profiles of the oral delayed release and sustained release mesalazine (5‐aminosalicylate, 5ASA) formulations (Asacol, Salofalk, Mesasal, Claversal, Pentasa) and pro‐drugs (sulfasalazine, olsalazine, balsalazide) used in the management of ulcerative colitis. Methods : Selected articles had: (1) adult healthy volunteers or patients with ulcerative colitis and (2) quantification of pharmacokinetic data to include, at a minimum, urinary excretion of total 5ASA [5ASA plus N‐Acetyl‐5ASA (N‐Ac‐5ASA)]. Data collection and analysis : Pharmacokinetic data ( T max , C max , AUC , urinary excretion, faecal excretion) of 5ASA, its major metabolite N‐Acetyl‐5ASA, total 5ASA, and the parent pro‐drug compounds was extracted. Main results : The summary results for urinary excretion of total 5ASA over 24–96 h in all subjects (either mean or median) were: sulfasalazine mean 11–33% or median 22%; olsalazine mean 14–31% or median 16–27%; balsalazide mean 12–35% or median 20%; Asacol mean 10–35% or median 18–40%; Pentasa mean 15–53% or median 23–34%; Salofalk, Mesasal and Claversal mean 27–56% or median 31–44%. The summary results for faecal excretion of total 5ASA over 24–96 h in all subjects (either mean or median) were: sulfasalazine mean 23–75% or median 38%; olsalazine mean 47–50% or median 17–36%; balsalazide mean 46% or median 22%; Asacol mean 40–64% or median 20–56%; Pentasa mean 12–51% or median 39–59%; Salofalk, Mesasal and Claversal mean 37–44% or median 23–35%. Conclusions : The systemic exposure to 5ASA, as measured by urinary excretion of total 5ASA, and the faecal excretion of total 5ASA is comparable for all oral mesalazine formulations and pro‐drugs. Thus, selection of a mesalazine therapy for the treatment of ulcerative colitis should be based on other factors such as efficacy, dose–response, toxicity of the parent compound and its metabolites, compliance issues related to dose forms and dosing schedules, and costs.