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Scand J Gastroenterol. 2001 Oct;36(10):1062-6.

Topical and oral anti-inflammatory activity of budesonide compared with oral prednisolone in an animal model using allergen-induced gut mucosal exudation of plasma as a marker.

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  • 1AstraZeneca R&D Lund, Sweden. Birgitta.Gustafsson@astrazeneca.com

Abstract

BACKGROUND:

Development of topically active glucocorticosteroids with minimal systemic effects is paramount in improving therapy in inflammatory bowel disease. Our experimental model in the rat has proved useful for assessing topical versus systemic anti-inflammatory potency of glucocorticosteroids on the inflamed gut.

METHODS:

Experiments were performed on allergen-sensitized perfused rat ileum in vivo. Mucosal exudation of plasma, induced by local allergen perfusion, was measured as the appearance of circulating 125I-labelled albumin in the gut lumen. Experiments compared the anti-exudative effects of oral budesonide (0.1 mg/kg) with oral prednisolone (1, 3.3 or 10 mg/kg) and saline, given by oral gavage 24 h prior to allergen challenge, and of topical budesonide (3 x 10(-5) mol/L) with saline, administered in the perfusate 4 h prior to allergen challenge. Systemic glucocorticosteroid activity was assessed by weighing thymus glands after sacrifice.

RESULTS:

Allergen-induced plasma exudation was significantly reduced by oral budesonide, oral prednisolone (dose-dependently) and topically applied budesonide; topical budesonide was effective within 4 h. While prednisolone significantly reduced the relative thymus weight at both 3.3 and 10 mg/kg, budesonide given orally, 0.1 mg/kg, or topically, 3 x 10(-5) mol/L, had no significant effect.

CONCLUSION:

Budesonide, administered orally or topically, shows higher selectivity for the gut mucosa than prednisolone and produces local anti-inflammatory responses comparable to prednisolone, without the accompanying systemic effects.

PMID:
11589379
[PubMed - indexed for MEDLINE]

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