title: Pharmacokinetic study for the establishment of bioequivalence of two inhalation treatments containing budesonide plus formoterol.
abstract: OBJECTIVE
  The aim of this study was to compare lung deposition and assess the bioequivalence of two formulations containing budesonide and formoterol and being delivered via Elpenhaler and Turbuhaler, respectively. A pharmacokinetic (PK) study was conducted.
  
  
  METHODS
  An open, randomized, two-sequence, two-period, crossover, single-dose study in 100 asthmatic patients under fasting conditions was performed. Wash out period was 6 days. Equivalence in lung deposition was assessed after a single inhalation of each treatment with concomitant oral administration of activated charcoal (40 g) to prevent gastrointestinal absorption of the drugs. Several PK parameters were estimated, the area under the drug concentration in plasma versus time curve (AUC0-t ) and the maximum drug concentration in plasma (Cmax ) being the primary response variables. Equivalent lung deposition was concluded if the 90% confidence interval (CI) for the Elpenhaler/Turbuhaler geometric mean ratio of AUC0-t and Cmax , for both drug substances fell within the regulatory limits (0.80-1.25).
  
  
  RESULTS
  Acceptance criteria were met. Equivalent lung deposition can be concluded. No statistically significant differences between treatments in the incidence of adverse events were found.
  
  
  CONCLUSIONS
  The formulations are bioequivalent regarding both rate and extent of absorption. The treatments were also well tolerated by the participating subjects.
authors.affiliation: ELPEN Pharmaceutical Co Inc., Pikermi, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Grekas
authors.forename: Katerina
authors.initials: K
authors.lastname: Athanassiou
authors.forename: Katerina
authors.initials: K
authors.lastname: Papataxiarchou
authors.forename: Simona
authors.initials: S
authors.lastname: Rizea Savu
authors.forename: Luigi
authors.initials: L
authors.lastname: Silvestro
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001249:Asthma / Q000097:blood / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018592:Cross-Over Studies; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D004983:Ethanolamines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013810:Therapeutic Equivalency; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate
keywords: bioequivalence; dry powder inhaler; formulation; pharmacokinetics; pulmonary deposition