The role of intracellular esterification in budesonide once-daily dosing and airway selectivity.

Background: Since their introduction in the 1970s, inhaled corticosteroids (ICSs) have been used to control airway inflammation associated with asthma. Budesonide is one of the ICSs recommended as first-line therapy for mild to moderate persistent asthma.

Objective: This article describes the esterification of budesonide and how it results in prolonged, location-specific retention of drug in the airways, allowing once-daily dosing.

Results: Studies conducted over the past decade have shown that budesonide forms reversible fatty acid esters within the cells of airway tissue, resulting in the formation of an intracellular depot pool of inactive drug. As the intracellular concentration of free budesonide decreases, these budesonide esters are hydrolyzed back to their active state. This process increases budesonide's retention in the airways, prolongs its duration of action, and lowers the risk of systemic effects.

Conclusions: By extending budesonide's local anti-inflammatory effect and increasing its airway selectivity, the esterification process appears to contribute to the drug's efficacy, particularly during once-daily administration. Reducing the number of required daily inhalations may increase patient compliance with asthma therapy, although this remains to be evaluated.