Zyics Mechanism of Action

Pharmacology: Pharmacokinetics: Absorption: In adults the systemic availability of budesonide following administration of Budesonide Nebulizing Suspension via a jet nebuliser is approximately 15% of the nominal dose and 40% to 70% of the dose delivered to the patients. A minor fraction of the systemically available drug comes from swallowed drug. The maximal plasma concentration, occurring about 10 to 30 min after start of nebulisation is approximately 4 nmol/L after a single dose of 2 mg.
Distribution: Budesonide has a volume of distribution of approximately 3 L/kg. Plasma protein binding averages 85-90%.
Biotransformation: Budesonide undergoes an extensive degree (=90%) of biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide and 16a-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of cytochrome P450.
Elimination: The metabolites of budesonide are excreted as such or in conjugated form mainly via the kidneys. No unchanged budesonide has been detected in the urine. It has high systemic clearance (approximately 1.2 L/min) in healthy adults, and the terminal half-life of budesonide after iv dosing averages 2-3 hours.
Linearity: The kinetics of budesonide are dose-proportional at clinically relevant doses.
In a study, 100 mg ketoconazole taken twice daily, increased plasma levels of concomitantly administered oral budesonide (single dose of 10mg) on average, by 7.8-fold. Information about this interaction is lacking for inhaled budesonide, but marked increases in plasma levels could be expected.
Paediatric population: Budesonide has a systemic clearance of approximately 0.5 L/min in 4-6 years old asthmatic children. Per kg body weight children have a clearance which is approximately 50% greater than in adults. The terminal half-life of budesonide after inhalation is approximately 2.3 hours in asthmatic children. This is about the same as in healthy adults. In 4-6 years old asthmatic children, the systemic availability of budesonide following administration of Budesonide Nebulizing Suspension via a jet nebuliser is approximately 6% of the nominal dose and 26% of the dose delivered to the patients. The systemic availability in children is about half of that in healthy adults.
The maximal plasma concentration, occurring approximately 20 min after start of nebulisation is approximately 2.4 nmol/L in 4-6 years old asthmatic children after a 1 mg dose. The exposure (Cmax and AUC) of budesonide following administration of a single 1 mg dose by nebulisation to 4-6 year old children is comparable to that in healthy adults given the same delivered dose by the same nebuliser system.