title: Lung deposition of BDP/formoterol HFA pMDI in healthy volunteers, asthmatic, and COPD patients.
abstract: BACKGROUND
  When inhaling medication, it is essential that drug particles are delivered to all sites of lung inflammation, including the peripheral airways. The aim of this study was to assess the lung deposition and lung distribution of beclomethasone dipropionate (BDP)/formoterol (100/6 microg), both dissolved in hydrofluoroalkane (HFA) and delivered by pressurized metered dose inhaler (pMDI) in healthy subjects, asthmatic, and chronic obstructive pulmonary disease (COPD) patients, to investigate how the in vitro characteristics of the formulation translate into the in vivo performance in diseases with different airway obstruction.
  
  
  METHODS
  Healthy volunteers (n = 8), persistent asthmatics (n = 8), and patients with stable COPD (n = 8) completed this open-label, single-dose parallel-group study. Each patient received one single treatment of four puffs of (99 m)Tc-labeled BDP/formoterol formulation. The correlation between particle size distribution of radioactivity and of the drugs in the radiolabeled formulation was validated. Intra- and extrapulmonary deposition, amount of exhaled drug, and the central to peripheral ratio (C/P) were calculated immediately after inhalation. Patients' lung function and pharmacokinetic parameters were also assessed up to 24 h post-dose.
  
  
  RESULTS
  The average lung deposition of BDP/formoterol was 34.08 +/- 9.30% (relative to nominal dose) in healthy subjects, 30.86 +/- 8.89% in asthmatics, and 33.10 +/- 8.90% in COPD patients. Extrathoracic deposition was 53.48% +/- 8.95, 57.64% +/- 9.92 and 54.98% +/- 7.01, respectively. C/P ratios of 1.42 +/- 0.32 in healthy subjects, 1.96 +/- 0.43 in asthmatics, and 1.94 +/- 0.69 for COPD patients confirmed drug distribution to all regions of the lungs. Forced expiratory volume in 1 sec (FEV(1)) increased in all groups after BDP/formoterol inhalation, but was more evident in the patient groups. No significant correlation between baseline lung function and drug deposition was observed. Formoterol, BDP, and beclomethasone 17 monopropionate (B17MP) plasma profiles were comparable between groups.
  
  
  CONCLUSIONS
  Inhalation of BDP/formoterol HFA (100/6 microg) produces high and homogeneous deposition of BDP and formoterol in the airways, regardless of pathophysiological condition.
authors.affiliation: University Hospital Antwerp , Edegem, Belgium.
authors.forename: Wilfried
authors.initials: W
authors.lastname: De Backer
authors.forename: Annick
authors.initials: A
authors.lastname: Devolder
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Poli
authors.forename: Daniela
authors.initials: D
authors.lastname: Acerbi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Monno
authors.forename: Christiane
authors.initials: C
authors.lastname: Herpich
authors.forename: Knut
authors.initials: K
authors.lastname: Sommerer
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Mariotti
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy; D001507:Beclomethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D016022:Case-Control Studies; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D010316:Particle Size; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D012129:Respiratory Function Tests; D014018:Tissue Distribution
chemical_list: D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D001507:Beclomethasone; D000068759:Formoterol Fumarate