Frenolyn Mechanism of Action

Pharmacotherapeutic group: Inhalation drugs for obstructive airway diseases. ATC Code: RO3B A02.
Pharmacology: Pharmacodynamics: Budesonide is a glucocorticosteroid with a high local anti-inflammatory effect.
The precise mechanism of action of glucocorticosteroids in the treatment of asthma is not fully understood. Anti-inflammatory actions, such as inhibited release of inflammatory mediators and inhibition of cytokine-mediated immune response are probably important. The activity of budesonide measured as its affinity for glucocorticosteroid receptors is approx. 15 times higher than that of prednisolone.
Budesonide has anti-inflammatory effects shown as reduced bronchial obstruction during both the early and the late phase of an allergic reaction.
Budesonide has been shown to decrease airway reactivity to histamine and methacholine in hyperreactive patients.
Studies have shown that the earlier budesonide treatment is initiated after the onset of asthma, the better lung function can be expected.
Studies in healthy volunteers with budesonide have shown dose-related effects on plasma and urinary cortisol. At recommended doses, budesonide causes significantly less effect on the adrenal function than prednisolone 10 mg, as shown by ACTH tests.
In children over the age of 3 years, no systemic effects have been detected with doses up to 400 micrograms per day. In the range 400 - 800 micrograms per day biochemical signs of a systemic effect may occur. With daily doses in excess of 800 micrograms such signs are common.
Asthma, like inhaled corticosteroids, can delay growth.
However, studies in children and adolescents who were treated with budesonide for a long period (up to 13 years) show that the patients reach the expected adult height.
Inhalation therapy with budesonide is effective in preventing exercise-induced asthma.
Pharmacokinetics: Absorption: Inhaled budesonide is rapidly absorbed. The peak plasma concentration is reached within 30 minutes after inhalation. In studies, the average deposition in the lungs after inhalation via different devices has been shown to be 25-35% of the metered dose. The systemic bioavailability is approximately 38% of the metered dose.
Distribution and metabolism: Plasma protein-binding is approx. 90%. The volume of distribution is approx. 3l/kg.
Budesonide undergoes an extensive degree (approximately 90%) first pass metabolism in the liver to metabolites with low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, is less than 1% of that of budesonide.
Elimination: Budesonide is eliminated through metabolism, catalysed primarily by the enzyme CYP3A4. The metabolites are excreted in the urine in unchanged or conjugated form. Only negligible amounts of unchanged budesonide are recovered in the urine. Budesonide has a high systemic clearance (approx. 1.2l/min), and the plasma half-life after intravenous administration is on average of 4 hours.
The pharmacokinetics of budesonide is proportional to the dose at relevant dosages.
The pharmacokinetics of budesonide in children and in patients with impaired renal function is unknown.
Exposure to budesonide may be increased in patients with hepatic disease.