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Comparison of the Oropharyngeal Deposition of Inhaled Ciclesonide and Fluticasone Propionate in Patients With Asthma
Author(s) -
Richter Kai,
Kanniess Frank,
Biberger Christian,
Nave Ruediger,
Magnussen Helgo
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004271094
Subject(s) - ciclesonide , fluticasone propionate , inhalation , metabolite , active metabolite , fluticasone , pharmacokinetics , asthma , medicine , chemistry , corticosteroid , pharmacology , anesthesia , inhaled corticosteroids
Ciclesonide is a novel inhaled corticosteroid that is converted in the lungs to its active metabolite, desisobutyryl‐ciclesonide (des‐CIC). The aim of this study was to compare the deposition of ciclesonide, as well as its conversion to des‐CIC, in the oropharyngeal cavity with fluticasone propionate (FP) following inhalation via hydrofluoroalkane‐propelled metered‐dose inhalers (HFA‐MDIs). Eighteen asthmatics inhaled ciclesonide 800 μg followed by FP 1000 μg or vice versa in an open, randomized, 2‐treatment, 2‐sequence study design. The oropharynx was washed out immediately and at 15, 30, 45, and 60 minutes after inhalation. Samples were analyzed for ciclesonide, des‐CIC, and FP using liquid chromatography with tandem mass‐spectrometric detection. Concentrationtime curves and area under the concentration‐time curve (AUC) were calculated for each drug. Ciclesonide and FP were recovered in almost all samples. Within 60 minutes after inhalation, the amounts of both ciclesonide and FP decreased sharply, and low residual levels were detected after 30 minutes. des‐CIC was detected in relatively low concentrations, with maximum concentration 30 minutes following inhalation. The AUC 0–60 min for ciclesonide (250.4 nmol•h/L) and des‐CIC (37.8 nmol•h/L) were found to be significantly lower compared with FP (636.2 nmol•h/L, P <.001). Approximately 50% less ciclesonide and 90% less metabolite were present in the oropharynx compared with FP. Less than 20% of the residual ciclesonide in the oropharynx was metabolized to des‐CIC. These findings indicate that oropharyngeal deposition of ciclesonide is only half that of FP following inhalation from an HFA‐MDI. Furthermore, there is little activation of ciclesonide to its active metabolite in the oropharynx, suggesting a decreased likelihood of inhaled ciclesonide‐associated oropharyngeal side effects.