Effects of plain and controlled-ileal-release budesonide formulations in experimental ileitis.
BACKGROUND
Budesonide combines a topical anti-inflammatory activity with high first-pass hepatic extraction. This study compared the effects of plain and controlled-ileal-release (CIR) formulations of budesonide on intestinal inflammation.


METHODS
Ileitis was induced in hamsters by an intraluminal injection of trinitrobenzene sulphonic acid. Inflammation was assessed histologically and by measuring mastocytosis and myloperoxidase activity. Adrenal-pituitary axis suppression was assessed by radio-immunoassay of plasma cortisol. Animals received budesonide (200 or 800 micrograms/kg/day), CIR budesonide (200 micrograms/kg/day), or placebo.


RESULTS
Plain budesonide (200 micrograms/kg/day) did not reduce intestinal inflammation despite significantly lowered plasma cortisol levels. Plain budesonide (800 micrograms/kg/day), on the other hand, significantly reduced intestinal inflammation but further decreased plasma cortisol levels. CIR budesonide (200 micrograms/kg/day) was as effective in reducing inflammation as plain budesonide (800 micrograms/kg/day).


CONCLUSIONS
CIR budesonide was significantly more effective in reducing intestinal inflammation than plain budesonide. These results suggest that the site of delivery influences the effectiveness of budesonide and that local (topical) rather than systemic action of this compound is primarily responsible for its anti-inflammatory effect.
Aron M. Rappaport Microcirculation Laboratory, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
A J
AJ
Boyd
I A
IA
Sherman
F G
FG
Saibil
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D019819:Budesonide; D006224:Cricetinae; D003692:Delayed-Action Preparations; D006854:Hydrocortisone / Q000097:blood; D007079:Ileitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007082:Ileum / Q000201:enzymology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000473:pathology; D008647:Mesocricetus; D009195:Peroxidase / Q000378:metabolism; D011282:Pregnenediones / Q000008:administration & dosage*; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D011282:Pregnenediones; D019819:Budesonide; D014302:Trinitrobenzenesulfonic Acid; D009195:Peroxidase; D006854:Hydrocortisone