EFFECTS OF PLAIN AND CONTROLLED-ILEAL-RELEASE BUDESONIDE FORMULATIONSIN EXPERIMENTAL ILEITIS

Background: Budesonide combines a topical anti-inflammatory activity w ith high first-pass hepatic extraction. This study compared the effect s of plain and controlled-ileal-release (CIR) formulations of budesoni de on intestinal inflammation. Methods: Ileitis was induced in hamster s by an intraluminal injection of trinitrobenzene sulphonic acid. Infl ammation was assessed histologically and by measuring mastocytosis and myeloperoxidase activity. Adrenal-pituitary axis suppression was asse ssed by radioimmunoassay of plasma cortisol. Animals received budesoni de (200 or 800 mu g/kg/day), CIR budesonide (200 mu g/kg/day), or plac ebo. Results: Plain budesonide (200 mu g/kg/day) did not reduce intest inal inflammation despite significantly lowered plasma cortisol levels . Plain budesonide (800 mu g/kg/day), on the other hand, significantly reduced intestinal inflammation but further decreased plasma cortisol levels. CIR budesonide (200 mu g/kg/day) was as effective in reducing inflammation as plain budesonide (800 mu g/kg/day). Conclusions: CIR budesonide was significantly more effective in reducing intestinal inf lammation than plain budesonide. These results suggest that the site o f delivery influences the effectiveness of budesonide and that local ( topical) rather than systemic action of this compound is primarily res ponsible for its anti-inflammatory effect.