Pharmacology: Pharmacodynamics: Budesonide, a synthetic corticosteroid, has potent glucocorticoid and weak mineralocorticoid activity. In studies, the activity of budesonide measured as its affinity for glucocorticosteroid receptors is approximately 15 times higher than affinity of prednisolone.
The exact mechanism of action relevant to therapeutic effects is not clearly known, but is believed to work by reduction number of mediator cells in the nasal mucosa (including basophils, eosinophils, T-helper cells, mast cells and neutrophils), decrease in nasal reactivity to allergens, and inhibition of the release of proteolytic enzymes and inflammatory mediators.
Pharmacokinetics: Absorption: After inhalation of budesonide, absorption is rapid and peak plasma concentrations are reached within 30 minutes. From the studies, approximately 25-35% of the budesonide given dose is deposited in the lungs after inhalation. The systemic bioavailability of budesonide has been estimated to 38%.
Distribution: Budesonide is approximately 85-90% bound to plasma protein. The volume of distribution is approximately 3 liters/kg.
Metabolism: Budesonide undergoes extensive (about 90%) first-pass metabolism by cytochrome P-450 (CYP) isoenzyme 3A4 in the liver. The 2 main metabolites, 6 β-hydroxybudesonide and 6 α-hydroxyprednisolone, are low glucocorticoid activity. They have less than 1% of affinity for glucocorticoid receptors than budesonide (parent compound).
Elimination: After administration by the inhalation route, budesonide has half-life 2-3 hours. Its metabolites are excreted by urine (approximately 60%) and feces.
At relevant dosages, the pharmacokinetics of budesonide are dose proportional.
In children and in patients with impaired renal function, the pharmacokinetics of budesonide are unknown but expose to budesonide may be higher in patients with liver disease.