Asthlon Mechanism of Action

Pharmacologic Classification: Corticosteroid.
Pharmacology: Pharmacokinetics: Absorption: The estimated daily infant dose was 0.3% of the daily maternal dose for both dose levels, and the average plasma concentration in infants was estimated to be 1/600th. In adults the systemic bioavailability of budesonide following administration of Budesonide suspension for nebulization via nebulizer is approximately 15% of the declared dose and 40-70% of the dose delivered to the patient. A small part of the systematically available dose comes from inhalation suspension that is allowed. The peak plasma concentration following administration of a single dose of 2 mg is achieved 10-30 minutes after the beginning of inhalation and is approximately 4 nmol/L. In children (4-6 years), the systemic bioavailability of budesonide after administration of Budesonide suspension for nebulization via nebulizer is approximately 6% of the declared dose and 26% of the dose administered to the patient. The peak plasma concentration following administration of a single dose of 1 mg is approximately 20 minutes after the beginning of inhalation and is approximately 2.4 nmol/L.
Distribution: The volume of distribution in adults is approximately 3 L/kg. Plasma protein binding is approximately 85-90%.
Metabolism: Budesonide undergoes extensive (90%) first pass biotransformation in the liver via CYP3A4 to metabolites a low glucocorticosteroid activity. The in-vitro activity of the main metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.
Excretion: The metabolites are excreted in unchanged or conjugated form predominantly via the kidneys. No unchanged budesonide is found in the urine. Budesonide has a high systemic clearance (approximately 1.2 liters/min) in healthy adults, and the elimination half-life following intravenous administration is approximately 2-3 hours. Budesonide has a systemic clearance of approximately 0.5 L/min in 4 to 6 year-old asthmatic children. Children have an approximately 50% higher clearance per kg body weight than adults. The half-life of budesonide following inhalation is about 2.3 hours in asthmatic children, which is roughly the same as in healthy adults.
Biotransformation: 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 CYP450.
Pharmacodynamics: Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect.
Topical anti-inflammatory effect: The exact mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions involving T cells, eosinophils and mast cells, such as inhibition of inflammatory mediator release and inhibition of cytokine-mediated immune response are probably important. The intrinsic potency of budesonide, measured as the affinity to the glucocorticoid receptor, is about 15 times higher than that of prednisolone.
A clinical study in asthmatics comparing inhaled and oral budesonide at similar plasma concentrations demonstrated statistically significant evidence of efficacy with inhaled but not oral budesonide compared with placebo. Thus, the therapeutic effect of conventional doses of inhaled budesonide may be largely explained by its direct action on the respiratory tract.
Budesonide has shown anti-anaphylactic and anti-inflammatory effects in provocation studies in animals and patients, manifested as decreased bronchial obstruction in the immediate as well as the late allergic reaction.
Exacerbations of asthma: Inhaled budesonide has been shown to effectively treat and prevent exacerbations of asthma in both children and adults.
Exercise-induced asthma: Therapy with inhaled budesonide, administered either as once or twice daily has been effective when used for prevention of exercise-induced bronchoconstriction. Budesonide has been shown to decrease airway reactivity to histamine and methacholine in hyperreactive patients.
Exacerbations of COPD: Several studies on nebulised budesonide, 4-8 mg/day has shown to effectively treat exacerbations of COPD.