Gut mucosal uptake and retention characteristics contribute to the high intestinal selectivity of budesonide compared with prednisolone in the rat.
BACKGROUND
Budesonide and prednisolone are both effective for the treatment of inflammatory bowel disease, but budesonide produces fewer adverse systemic effects. High first-pass hepatic inactivation of budesonide partially explains its favourable ratio between topical and systemic activity, but it is probable that its uptake and retention in intestinal target tissues are also contributory.


OBJECTIVE
To compare the uptake and retention of radio-labelled budesonide and prednisolone in rat ileal mucosa in vivo.


METHODS
3H-Budesonide and 3H-prednisolone were applied for 10 min directly to a perfused segment of rat ileum in vivo, followed by saline lavage every 10 min. Steroid uptake into the mucosa and submucosa was assessed at 20 min and 4 h. The uptake of budesonide was also measured in allergen-challenged animals vs. saline-challenged controls to assess whether inflammation of the mucosa with ongoing plasma exudation would impair its uptake.


RESULTS
Budesonide was better absorbed into ileal tissue (15-fold at 20 min) than prednisolone and better retained (50-fold at 4 h) after topical administration. The uptake of budesonide was not impaired by exudation processes following allergen challenge.


CONCLUSIONS
The higher uptake and retention characteristics of budesonide in gut mucosa should contribute to its greater intestinal selectivity compared with that of prednisolone.
Miller-Larsson
A
A
AstraZeneca R&D Lund, Lund, Sweden. anna.miller-larsson@astrazeneca.com
Gustafsson
B
B
Persson
C G
CG
Brattsand
R
R
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D019819:Budesonide / Q000493:pharmacokinetics*; D005938:Glucocorticoids; D007082:Ileum / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D011239:Prednisolone / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D014316:Tritium; D019819:Budesonide; D011239:Prednisolone