| Indication |
For the treatment of mild to moderate active Crohn's disease. Also
for the treatment of asthma, non-infectious rhinitis (including hay
fever and other allergies), and for treatment and prevention of nasal
polyposis. |
| Pharmacodynamics |
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. |
| Mechanism of action |
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. |
| Absorption |
Absorption is complete following oral administration. |
| Volume of distribution |
- 3 L/kg [asthmatic children 4 to 6 years of age]
|
| Protein binding |
85-90% |
| Metabolism |
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 (<1/100) in relation to that of the parent
compound. |
| Route of elimination |
Budesonide is excreted in urine and feces in the form of metabolites. |
| Half life |
2.0 and 3.6 hours |
| Clearance |
- 0.5 L/min [Athmatic children 4 to 6 years of age]
|
| Toxicity |
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. |
