B Gustafsson

Publications (3)7.81 Total impact

• Article: Gut mucosal uptake and retention characteristics contribute to the high intestinal selectivity of budesonide compared with prednisolone in the rat.

  A Miller-Larsson, B Gustafsson, C G Persson, R Brattsand
  [show abstract] [hide abstract]
  ABSTRACT: 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. To compare the uptake and retention of radio-labelled budesonide and prednisolone in rat ileal mucosa in vivo. 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. 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. The higher uptake and retention characteristics of budesonide in gut mucosa should contribute to its greater intestinal selectivity compared with that of prednisolone.
  Alimentary Pharmacology & Therapeutics 01/2002; 15(12):2019-25. · 3.77 Impact Factor
• Article: 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.

  B Gustafsson, A Miller-Larsson, C G Persson
  [show abstract] [hide abstract]
  ABSTRACT: 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. 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. 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. 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.
  Scandinavian Journal of Gastroenterology 11/2001; 36(10):1062-6. · 2.02 Impact Factor
• Article: Allergen-induced mucosal exudation of plasma into rat ileum and its inhibition by budesonide.

  B Gustafsson, C G Persson
  [show abstract] [hide abstract]
  ABSTRACT: Exudation of plasma across the airway mucosa is a specific defence/inflammatory response finely regulated by mediators and (in rodents) a capsaicin-sensitive innervation. This study examines plasma exudation responses to endointestinal challenges and effects of a glucocorticoid. The ileum of anesthetized rats was catheterized and ligated at two points 10 cm apart for mucosal challenge (0.5 ml) and repeated lavages (5 ml). Lavage fluid levels of the plasma tracer 125I-albumin, previously injected intravenously, showed a stable, low base line greater than 2 h. Challenge with mediators (10(-5) M bradykinin, 10(-5)-10(-3) M serotonin, 10(-6)-10(-4) M histamine, 2.10(-9)-2.10(-7) M leukotriene D4 (LTD4), or 10(-5)-10(-3) M capsaicin did not increase luminal radioactivity. However, allergen (10(-6) M ovalbumin, in previously sensitized animals) produced prompt mucosal exudation of 125I-albumin, peaking within 30 min (p less than 0.001) and returning to base line within 90 min. Separate experiments suggested that absorption was not increased during the mucosal exudation. The glucocorticoid budesonide (10-1000 micrograms/kg given by gavage 24 h before challenge) dose-dependently inhibited the allergen-induced exudation (p less than 0.01). The route of administration and the antiexudative versus the systemic potency (reduced thymus weight) suggest the possibility of a topical action of budesonide. We conclude that endointestinal allergen challenge produces reversible and glucocorticoid-inhibitable exudation of plasma across the mucosa. It appears less likely that bradykinin, serotonin, histamine, LTD4, or a capsaicin-sensitive innervation is involved in producing this exudative effect.
  Scandinavian Journal of Gastroenterology 08/1992; 27(7):587-93. · 2.02 Impact Factor