Olsalazine-Related Diarrhoea: Does Rat Intestine Adapt in Vivo?

Abstract

Diarrhoea may occur in up to 10% of patients with ulcerative colitis treated with olsalazine, the azo-linked dimer of 5-aminosalicylic acid. However, this symptom often disappears despite continued drug medication. To examine reversibility of and adaption to olsalazine effects on intestinal absorption, rats were fed olsalazine (4mg/l00g body weight/day) for 0 (controls), 12, 24, and 32 days. Jejunal, ileal, and colonic loops were perfused in situ with buffer or olsalazine (11.6 mM) in a pendular perfusion system. Water and electrolyte absorption was inhibited in all intestinal segments (p < 0.001). In the proximal small intestine, however, sodium absorption was inhibited by 61%, whereas chloride and potassium absorptions were turned into net secretion. In contrast, in ileal and colonic segments sodium, chloride, and potassium absorptions were turned into a net secretion. All inhibitory effects were reversible within a short time. Intestinal absorption remained inhibitable compared with controls (p = not significant) after chronic administration of olsalazine even for 1 month. Jejunal monosaccharide absorption was not altered by acute olsalazine perfusion. In the ileum, glucose absorption was significantly inhibited, but the inhibitory capacity of acute olsalazine application decreased significantly (p < 0.05) depending on duration of olsalazine pretreatment (51% (controls) versus 38% (32 days)). These results point to a complex, acute, but fully reversible effect of olsalazine on intestinal passive and chloride-coupled absorptive processes. Since a mucosal adaption to these diarrhogenic effects does not occur, the resulting increase in fluid load on the diseased colon may be important in the pathogenesis of olsalazine-related diarrhoea.

Key Words:

• Adaption
• diarrhoea
• intestinal perfusion
• olsalazine
• reversibility
• ulcerative colitis
• therapy