Contribution to safe anti-inflammatory therapy with indomethacin

Non-steroidal anti-inflammatory drugs possess not only therapeutic but also adverse effects, mainly on the gastrointestinal tract. The aim of this pilot study was to establish the ulcerogenic dose caused by daily administration of indomethacin to male Lewis rats. Further, the model of rat adjuvant arthritis (AA) was used to evaluate the protective effect of stobadine dipalmitate against indomethacin-induced gastroenteropathy. Indomethacin was administered subcutaneously in the daily dose of 5, 7, 10, 20 and 30 mg/kg b.w. Survival of the animals and damage of gastric and intestinal mucosa were monitored, and some biochemical parameters were determined. In AA rats stobadine dipalmitate was administered orally in the daily dose of 15 mg/kg. For the chronical experiments on AA rats the subcutaneous indomethacin dose of 5 mg/kg was selected as the therapeutic dose and the dose of 7 mg/kg was chosen as the adequate dose for gastropathy induction. The additive adverse effect of arthritis induction and indomethacin administration was demonstrated on the basis of gastric mucosa damage observations. The supposed stobadine gastro-protection was not confirmed.