Olsalazine Induced Secretion in Rabbit IIeal Mucosa

Abstract

Olsalazine has been observed to induce diarrhoea in 4.9% of patients. In vivo trials in rat ileum and colon suggest stimulation of secretion by olsalazine. The in vitro effect of olsalazine was examined on active anion secretion by rabbit distal ileum compared to sulphasalazine and 5-aminosalicylic acid (5-ASA). Rabbit terminal ileal strips were mounted in Ussing chambers, and the mucosal and serosal surfaces were selectively exposed to 3.0, 5.0, 1.0, 0.1 and 0.001 mM of olsalazine, sulphasalazine and 5-ASA. The maximal short circuit current (I_sc, a measure of active anion secretion) was determined for each concentration. Olsalazine significantly stimulated anion secretion at concentrations above 0.001 mM with a more pronounced effect (approximate ED₅₀ of 0.5 mM) when added to the mucosal surface. In contrast, sulphasalazine and 5-ASA demonstrated no secretory effect. Additional studies of transmucosal fluxes and chemical mediation of these effects are in progress and will be reported. Olsalazine stimulated anion secretion in distal rabbit ileum at therapeutically relevant concentrations.