title: Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Albuterol (Salbuterol) Multi-dose Dry-Powder Inhaler and ProAir(®) Hydrofluoroalkane for the Treatment of Persistent Asthma: Results of Two Randomized Double-Blind Studies.
abstract: OBJECTIVE
  Metered-dose inhalers require patients to coordinate inhalation with actuation. The present albuterol multi-dose dry-powder inhaler (mDPI) does not require patients to coordinate inspiration with actuation, thereby simplifying delivery of albuterol to the lungs. The aim of the present study was to compare the efficacy, pharmacokinetics, pharmacodynamics, extrapulmonary pharmacodynamics, and safety of albuterol (salbuterol) delivered via a ProAir® hydrofluoroalkane (HFA) metered-dose inhaler and an mDPI.
  
  
  METHODS
  Two double-blind, randomized, double-dummy, crossover, multicenter, placebo-controlled studies in persistent asthma patients were conducted. Study 1: 47 adult patients were treated with cumulative doses of albuterol mDPI or ProAir HFA (90 µg/inhalation; 1 + 1 + 2 + 4 + 8 inhalations) or placebo. Study 2: 71 patients aged ≥12 years were randomly assigned to receive 90 or 180 μg of albuterol mDPI or ProAir HFA, or placebo. Primary efficacy endpoints were baseline-adjusted forced expiratory volume in 1 s (FEV1) at 30 min (30-min FEV1) after each cumulative dose (Study 1) and FEV1 area under the effect curve over 6 h (FEV1 AUEC0-6) after dosing (Study 2).
  
  
  RESULTS
  Study 1: differences, with corresponding 90% confidence intervals, between albuterol mDPI and ProAir HFA in FEV1 after each cumulative dose and in FEV1 AUEC0-6 after the final dose were within pre-established equivalence limits. The difference in FEV1 at high vs. low doses was significant for both active treatments (p < 0.0001). Active treatments were similar in systemic exposure, extrapulmonary pharmacodynamics, and safety. Study 2: mean FEV1 AUEC0-6 was significantly greater than for placebo for both doses of albuterol mDPI and ProAir HFA (p < 0.0001). Albuterol mDPI was comparable to ProAir HFA at 90 and 180 µg. Both study treatments were generally well tolerated.
  
  
  CONCLUSIONS
  The bronchodilatory efficacy and pharmacokinetic/pharmacodynamic profiles of albuterol mDPI and ProAir HFA are comparable, with a safety profile consistent with that of inhaled albuterol.
authors.affiliation: Clinical Research Institute of Southern Oregon, PC, 3860 Crater Lake Avenue, Suite B, Medford, OR, 97507, USA. ekerwin@allergyasthmaso.com.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Kerwin
authors.affiliation: Teva Branded Pharmaceuticals R&D Inc., Frazer, PA, USA.
authors.forename: Herminia
authors.initials: H
authors.lastname: Taveras
authors.affiliation: Teva Branded Pharmaceuticals R&D Inc., Frazer, PA, USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Iverson
authors.affiliation: Teva Branded Pharmaceuticals R&D Inc., Frazer, PA, USA.
authors.forename: Denise
authors.initials: D
authors.lastname: Wayne
authors.affiliation: Teva Branded Pharmaceuticals R&D Inc., Frazer, PA, USA.
authors.forename: Tushar
authors.initials: T
authors.lastname: Shah
authors.affiliation: , Maple Glen, PA, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Lepore
authors.affiliation: Northeast Medical Research Associates, North Dartmouth, MA, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Miller
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D058995:Dry Powder Inhalers; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D012129:Respiratory Function Tests; D055815:Young Adult; D005466:Fluorocarbons
chemical_list: D000420:Albuterol; D001993:Bronchodilator Agents; D006845:Hydrocarbons, Fluorinated; C094049:apaflurane; D005466:Fluorocarbons