Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties
Pharmacotherapeutic group: Intestinal anti-inflammatory agents, corticosteroids acting locally
ATC code: A07EA06

The exact mechanism of action of budesonide in the treatment of ulcerative colitis/procto-sigmoiditis is not fully understood. Data from clinical pharmacology studies and controlled clinical trials strongly indicate that the mode of action of budesonide is predominantly based on a local action in the gut. Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect. At a dosage of 2 mg budesonide, applied rectally, budesonide leads to practically no suppression of the hypothalamus-hypophysis-adrenal cortex axis.
Budeson rectal foam investigated up to the daily dosage of 4 mg budesonide showed virtually no influence on the plasma cortisol level.

Pharmacokinetic Properties

5.2.   Pharmacokinetic properties

Absorption:
After oral application the systemic availability of budesonide is about 10%. After rectal administration the areas under the concentration time curves are about 1.5-fold higher than in historical controls considering the identical oral budesonide dose. Peak levels are obtained after an average of 2-3 hours after administering Budeson rectal foam.

Distribution:
Budesonide has a high volume of distribution (about 3 l/kg). Plasma protein binding averages 85 -90%.

Biotransformation:
Budesonide undergoes extensive biotransformation in the liver (approximately 90 %) to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6 β-hydroxybudesonide and 16 α-hydroxyprednisolone, is less than 1 % of that of budesonide.

Elimination:
The average elimination half-life is about 3 - 4 hours. The mean clearance rate is about 10 - 15 l/min for budesonide, determined by HPLC-based methods.

Spread:
A scintigraphic investigation with technetium-marked Budeson rectal foam on patients with ulcerative colitis showed that the foam spreads out over the entire sigmoid.

Specific patient populations (liver diseases):
Dependent on the type and severity of liver diseases the metabolism of budesonide might be decreased.