title: Two-dimensional and three-dimensional imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers.
abstract: Drug deposition is an important factor that contributes to safety and efficacy outcomes of inhaled steroid therapy. Ciclesonide is a nonhalogenated, inhaled corticosteroid under investigation for the treatment of asthma. Therefore, this study was performed to assess lung deposition of ciclesonide. Technetium-99m (99mTc)-labeled ciclesonide (where the 99mTc-label is physically dissolved in the ciclesonide-hydrofluoroalkane [HFA] solution aerosol) inhaled by healthy volunteers was analyzed by two-dimensional (2-D) and three-dimensional (3-D) imaging to determine lung deposition. Six healthy volunteers inhaled one puff of 40 microg (exactuator, equivalent to 50 microg ex-valve) ciclesonide for 2-D imaging, and two healthy volunteers inhaled 10 puffs of 40 microg ciclesonide for 2-D and 3-D imaging. The ciclesonide aerosol was administered via metered-dose inhaler (MDI) containing HFA-134a as propellant. The ex-actuator mean (+/- standard deviation) deposition of ciclesonide in the lungs was higher (52% +/- 11%) than in the mouth/pharynx (38% +/- 14%). Two-dimensional and 3-D imaging showed that ciclesonide reached all regions of the lung. Mean percent deposition in peripheral regions (47% and 34%) was higher than in lower central regions (17% and 30%), as revealed by 3-D and 2-D imaging, respectively. Inhalation of up to 400 microg of ciclesonide produced no drug-related side effects. In conclusion, ciclesonide administered via metered-dose inhaler using HFA-134a as a propellant provided high lung deposition (>50%), greater distribution throughout peripheral regions of the lungs, and relatively low oropharyngeal deposition.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108-5128, USA. cleach@lrri.org
authors.forename: Chet L
authors.initials: CL
authors.lastname: Leach
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bethke
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Boudreau
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Hasselquist
authors.forename: Anton
authors.initials: A
authors.lastname: Drollmann
authors.forename: Patricia
authors.initials: P
authors.lastname: Davidson
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Wurst
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000335:Aerosol Propellants; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009960:Oropharynx / Q000378:metabolism; D011282:Pregnenediones / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D005466:Fluorocarbons
chemical_list: D000335:Aerosol Propellants; D005938:Glucocorticoids; D006845:Hydrocarbons, Fluorinated; D011282:Pregnenediones; C094049:apaflurane; D005466:Fluorocarbons; C120481:ciclesonide