The exact mechanism of action of budesonide in the treatment of Crohn's disease is not fully understood. However, being a glucocorticosteroid, budesonide has a high local anti-inflammatory effect.
Budesonide is a synthetic corticosteroid used in Crohn's disease to decrease the symptoms and inflammation associated with the disease, especially at times of flare up. Budesonide has a high topical glucocorticosteroid (GCS) activity and a substantial first pass elimination. The formulation contains granules which are coated to protect dissolution in gastric juice, but which dissolve at pH >5.5, ie, normally when the granules reach the duodenum. Thereafter, a matrix of ethylcellulose with budesonide controls the release of the drug into the intestinal lumen in a time-dependent manner.
Following absorption, budesonide is subject to high first pass metabolism (80-90%). In vitro experiments in human liver microsomes demonstrate that budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6b-hydroxy budesonide and 16a- hydroxy prednisolone. The glucocorticoid activity of these metabolites is negligible (
Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.