title: Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers.
abstract: OBJECTIVE
  Budesonide formoterol (BF) Spiromax® is a breath-actuated dry-powder inhaler designed to deliver similar combinations of budesonide and formoterol as Symbicort® Turbohaler®. We performed two studies to demonstrate pharmacokinetic (PK) equivalence of BF Spiromax with BF Turbohaler.
  
  
  METHODS
  Two single-center, open-label, randomized, 5-period crossover studies were performed. The first study compared BF Spiromax 160/4.5 μg with BF Turbohaler 200/6 μg, while the second study compared BF Spiromax 320/9 μg with BF Turbohaler 400/12 μg. All treatments were administered with and without charcoal. PK parameters were calculated by measuring plasma drug concentrations from blood samples taken pre-dose and up to 24 hours post-dose.
  
  
  RESULTS
  In each study, 90 healthy volunteers were randomized. Bioequivalence of BF Spiromax with BF Turbohaler was demonstrated for budesonide and formoterol (AUC0-t and Cmax (90% confidence intervals of the geometric mean between-device ratios for both parameters were within the predefined range of 0.80-1.25 in both studies)). Equivalence was observed without use of charcoal (overall absorption post-inhalation) and with charcoal (pulmonary absorption). There were no major differences between treatments in tmax for either budesonide or formoterol. All study treatments were well tolerated (one treatment-emergent adverse event (TEAE) in the medium-dose study and four TEAEs in the high-dose study).
  
  
  CONCLUSIONS
  These studies indicate that BF Spiromax (±charcoal block) is bioequivalent to BF Turbohaler with respect to the PK parameters assessed. Single doses of BF Spiromax were well tolerated; the overall safety profile of BF Spiromax and BF Turbohaler was similar.
authors.forename: Lori
authors.initials: L
authors.lastname: Weisfeld
authors.forename: Youyi
authors.initials: Y
authors.lastname: Shu
authors.forename: Tushar P
authors.initials: TP
authors.lastname: Shah
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002606:Charcoal; D018592:Cross-Over Studies; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D004867:Equipment Design; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D005938:Glucocorticoids; D002606:Charcoal; D019819:Budesonide; D000068759:Formoterol Fumarate