Effects of sulphasalazine and disodium azodisalicylate on colonic PGE₂ concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium axodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E₂ concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE₂ concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18 000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p < 0.001). In all healthy volunteers PGE₂ concentrations decreased slightly (p < 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE₂ concentrations to values above normal levels (p < 0.05) which returned to pretrial values (p < 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE₂ in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE₂ concentrations were normalised by sodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.