Ciclesonide: A Closer Look at its Systemic and Oropharyngeal Safety Profile

Abstract

Inhaled corticosteroids (ICS) are recommended first-line therapy for patients with asthma of all severities. Prolonged exposure to high-dose ICS can cause systemic and oropharyngeal adverse events. Minimizing ICS-related adverse events by selecting an ICS with an improved safety profile may increase patients' adherence to their asthma treatment. Ciclesonide, a novel ICS currently under development, is a parent compound that is converted in the lungs by endogenous esterases to its active metabolite, desisobutyryl-ciclesonide. Reported data suggest that ciclesonide is well tolerated, with no observed effect on hypothalamic-pituitary-adrenal (HPA)-axis function and a low incidence of oropharyngeal adverse events (comparable with placebo). These safety benefits, observed in children and adults with asthma, may be due to ciclesonide's favorable pharmacokinetic/pharmacodynamic properties. The lack of HPA-axis function suppression may be due to the low oral bioavailability, high serum protein binding and rapid apparent systemic clearance reported with desisobutyryl-ciclesonide. The low incidence of oropharyngeal adverse events may be attributed to the low oral deposition of ciclesonide in the oropharynx and its limited conversion to desisobutyryl-ciclesonide. The favorable safety profile of ciclesonide suggests a conferred benefit to asthma patients treated with this novel ICS.