title: The pharmacodynamics, pharmacokinetics, safety and tolerability of inhaled fluticasone furoate and vilanterol administered alone or simultaneously as fluticasone furoate/vilanterol.
abstract: To investigate the potential for systemic pharmacokinetic (PK) and pharmacodynamic (PD) interactions between inhaled fluticasone furoate (FF) and vilanterol (VI) when delivered simultaneously via the ELLIPTA™ dry powder inhaler (DPI).
  
  
  
  Randomized, double-blind, placebo-controlled, crossover study. Healthy subjects (n = 16) received single doses of FF (800 mcg), VI (100 mcg), FF/VI (800/100 mcg), and placebo. Endpoints measured were systemic PD (FF: serum cortisol; VI: heart rate), FF and VI plasma PK (0-48 hours), pharyngometry, inhalation and breath hold profiles and safety assessments.
  
  
  
  Treatment differences [90% confidence interval (CI)] in weighted mean serum cortisol (0-24 hours) were 12.3% [4.4, 20.9] (FF/VI vs. FF) and for maximum heart rate (0-4 hours) were -1.2 bpm [-4.6, 2.1] (FF/VI vs. VI). When delivered simultaneously, FF and VI systemic exposures were slightly lower (<20%) versus delivery of either agent alone (although this was not a formal bioequivalence study). In vitro simulation of selected inhalation profiles and modeling supported the PK and PD findings. FF/VI, FF and VI were well tolerated with an AE incidence comparable to placebo.
  
  
  
  These results suggest there was a slight PK interaction and no PD interactions of concern between inhaled FF and VI when delivered simultaneously via the ELLIPTA DPI in healthy subjects.
authors.affiliation: GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts, UK.
authors.forename: Rodger
authors.initials: R
authors.lastname: Kempsford
authors.affiliation: GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts, UK.
authors.forename: Ann
authors.initials: A
authors.lastname: Allen
authors.affiliation: GlaxoSmithKline, Gunnels Wood Road, Stevenage, Herts, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bareille
authors.affiliation: GlaxoSmithKline, Ware, Hertfordshire, UK.
authors.forename: Melanie
authors.initials: M
authors.lastname: Hamilton
authors.affiliation: GlaxoSmithKline, Stockley Park West, Uxbridge, Middlesex, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Cheesbrough
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001592:Benzyl Alcohols / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002722:Chlorobenzenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D058995:Dry Powder Inhalers; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009517:New South Wales; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D001592:Benzyl Alcohols; D015415:Biomarkers; D001993:Bronchodilator Agents; D002722:Chlorobenzenes; D004338:Drug Combinations; D005938:Glucocorticoids; C550468:vilanterol; C523187:fluticasone furoate; D006854:Hydrocortisone
keywords: fluticasone furoate; pharmacodynamics; pharmacokinetics; vilanterol