Avacort Mechanism of Action

ATC Code: R03B A02.
Pharmacology: Pharmacodynamics: Budesonide is a glucocorticosteroid which possesses a high local anti-inflammatory action, with a lower incidence and severity of adverse effects than those seen with oral corticosteroids.
Pharmacokinetics: Absorption: Following oral inhalation via Avacort HFA 200mcg Metered Dose Inhaler, peak plasma concentrations of budesonide (4.0 nmol/L after a dose of 800 μg) occur within 30 minutes. Maximum plasma concentration and area under the plasma concentration time profile increase linearly with dose, but are slightly (20-30%) higher following repeated doses (3 weeks treatment) than after a single dose. Lung deposition is estimated to 34% ±10% of the metered dose (arithmetic mean ± SD), while 22% will be retained in the mouthpiece and the rest (approximately 45% of the metered dose) will be swallowed.
The maximal plasma concentration after inhalation of 1 milligram budesonide is about 3.5 nmol/L and is reached after about 20 minutes.
Distribution: Budesonide has a volume of distribution of approximately 3 L/kg. Plasma protein binding averages 85-90%.
Metabolism: Budesonide undergoes an extensive degree (approximately 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 16α-hydroxyprednisolone, is less than 1% of that of budesonide. The metabolism of budesonide is primarily mediated by CYP3A, a subfamily of cytochrome P450.
Excretion: The metabolites of budesonide are excreted as such or in conjugated form mainly via kidneys. No unchanged budesonide has been detected in the urine. Budesonide has high systemic clearance (approximately 1.2 L/min), and the terminal half-life of budesonide after iv dosing averages 2-3 hours.
Paediatric safety data: 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.