Lower oropharyngeal deposition of inhaled ciclesonide via hydrofluoroalkane metered-dose inhaler compared with budesonide via chlorofluorocarbon metered-dose inhaler in healthy subjects

摘要: Inhaled corticosteroids may cause oropharyngeal side effects if deposited in the oropharynx active form. Ciclesonide, an inhaled corticosteroid with low glucocorticoid receptor affinity, is activated primarily lung by esterases to metabolite, desisobutyryl-ciclesonide (des-CIC), high affinity. We studied deposition of ciclesonide, des-CIC, and budesonide. In open-label, randomized, two-treatment (administered sequence), five-period study, 18 healthy subjects received 800 μg (ex-valve) ciclesonide via a hydrofluoroalkane-pressurized, metered-dose inhaler followed budesonide (Pulmicort) chlorofluorocarbon-pressurized, (four puffs 200 μg each, ex-valve) or vice versa. Oropharyngeal cavity rinsing was performed immediately, 15, 30, 45, 60 min after inhalation (one per study period), solutions were analyzed using liquid chromatography tandem mass spectrometric detection. Ciclesonide detected most wash samples. Maximal concentration each reached immediately post-inhalation; maximal concentrations des-CIC 30% 0.67%, respectively, decreased rapidly within 15 min post-inhalation, less thereafter. Less than 10% residual converted des-CIC. The molar dose-adjusted amount 4% (P < 0.0001). There no significant adverse events. more one order magnitude lower that when administered respective inhalers. This explain frequency clinical studies.