Azodisalicylate (Olsalazine) in the treatment of active ulcerative colitis. A placebo controlled clinical trial and assessment of drug disposition

The efficacy, safety and disposition of azodisalicylate, (ADS, Olsalazine) was assessed in patients with left-sided ulcerative colitis (UC) or proctitis in a double-blind placebo controlled trial. Thirty patients with a mild-to-moderate attack of UC were randomly allocated to ADS capsules 1 g (b.d.) or placebo for 6 weeks; other therapy was ceased. Patients were reviewed weekly and plasma, urine and faecal concentrations of ADS and its metabolites were determined by high performance liquid chromatography (HPLC). Sigmoidoscopy and biopsy were repeated at 6 weeks. Four patients receiving placebo and two receiving ADS were withdrawn because of diarrhoea. Five patients known to be allergic to sulphasalazine had no adverse reactions to ADS. Good clinical response was found in six patients receiving ADS and in two receiving placebo (P= 0.11). Improvement in sigmoidoscopic findings and histological appearance of rectal biopsies was also seen more frequently in ADS-treated patients. Plasma concentrations of ADS were significantly higher in patients who improved. Faecal ADS, 5-ASA and acetyl-5-ASA varied widely and showed no correlation with response. ADS showed an advantage over placebo which needs to be confirmed by further studies; it was safe in sulphasalazine-sensitive patients but appeared to cause watery diarrhoea in two patients.