TOPICAL ANTICOLITIC EFFICACY AND SELECTIVITY OF THE GLUCOCORTICOID BUDESONIDE IN A NEW MODEL OF ACETIC ACID-INDUCED ACUTE COLITIS IN THE RAT

Aims: To study the effect of local or parenteral administration of the glucocorticoid budesonide in the acetic acid-induced colitis model in the rat. Methods: Colitis was induced in an exteriorized colonic segm ent by administration of 4% acetic acid for 15 s. Four days later, thi s colonic segment with colitis was examined using a morphological scor ing system, and measurements of myeloperoxidase activity and of plasma exudation into the colonic segment. The experimental colitis showed m orphological similarities to human ulcerative colitis, with 3-fold inc rease in myeloperoxidase activity and 6-fold increase in the plasma ex udation. Budesonide in different doses administered for 3 days, starti ng one day after acetic acid instillation, prevented the development o f colitis in a dose-dependent manner. The best effect of budesonide on the morphological score was achieved after local treatment at a dose of 10(-5) m twice daily (76% reduction compared with a control colitis group) and parenteral treatment with 0.75 mg/kg (80% reduction). Thes e doses also normalized myeloperoxidase activity and significantly red uced the plasma exudation. The systemic effects of the drug were most pronounced in the group treated with parenteral budesonide. This group showed the greatest reduction in body weight and a significant reduct ion of the weight of adrenal glands and spleen (as compared to control s). Thymus weight in animals treated systemically was significantly lo wer than in locally treated animals. In the group treated with local b udesonide the weight of adrenals was reduced. However, the weights of spleen and thymus were not reduced and the reduction of the body weigh t was even less than in the control group. Conclusion: Local treatment with budesonide at a dose of 10(-5) m (0.17 mg/kg if completely absor bed, but only 0.03 mg/kg with 15% bioavailability on colonic applicati on) was as effective as parenteral treatment at a dose of 0.75 mg/kg i n the attenuation of acetic acid-induced colitis in the rat, but resul ted in minor systemic side-effects.