Comparative analysis of the in vitro prosecretory effects of balsalazide, sulfasalazine, olsalazine, and mesalamine in rabbit distal ileum.

ABSTRACT

BACKGROUND: The aminosalicylates remain foundation therapy for mild-to-moderate ulcerative colitis. Pro-drug 5-aminosalicylic acid (5-ASA; mesalamine) formulations have been developed to prevent 5-ASA from the proximal absorption and release of mesalamine, to decrease inflammation, and to improve colonic absorption. Clinically, pro-drugs such as olsalazine have been associated with dose-dependent diarrhea, which was likely secondary to ileal secretion induced by the azo linkages, in 17% of patients. The present study tested the hypothesis that the use of all compounds with azo linkages leads to increased secretion. METHODS: Intestinal tissue was randomly assigned to serve as controls or to receive brush border addition of equimolar concentrations of the compounds, and the change in short-circuit current was measured. RESULTS: Mesalamine did not induce secretion at any dose. Mean equivalent doses (0.1 to 10 mM) of balsalazide (range, 6.3 +/- 1.5 to 16.7 +/- 1.3 microA/cm2), olsalazine (range, 2.0 +/- 1.0 to 7.0 +/- 2.1 microA/cm2), and sulfasalazine (3.2 +/- 1.1 to 6.2 +/- 1.5 microA/cm2) significantly stimulated (P < 0.001) secretion. The values for the effective dose that is half the maximal dose for secretion induced by sulfasalazine, olsalazine, and balsalazide were 0.4, 0.7, and 0.9 mM, respectively. CONCLUSIONS: This study is the first to demonstrate that the use of pro-drugs with azo bonds leads to increased ileal secretion at equimolar concentrations of 5-ASA. Physicians should use caution when providing higher doses of the pro-drug forms of 5-ASA to their patients, as this could lead to increased diarrhea.