title: Pharmacokinetic comparison of inhaled fixed combination vs. the free combination of beclomethasone and formoterol pMDIs in asthmatic children.
abstract: OBJECTIVE
  The fixed combination of beclomethasone (BDP) and formoterol pressurized metered dose inhaler (pMDI) (Foster®, Chiesi Farmaceutici) is being developed in the lower strength (BDP/formoterol: 50/6 μg) to provide an appropriate dosage for children with asthma. The aim of this work was to investigate the systemic bioavailability of beclomethasone-17-monoproprionate (B17MP, the active metabolite of BDP) and formoterol after single inhalation of Foster® pMDI 50/6 μg vs. the free combination of BDP and formoterol pMDIs in asthmatic children.
  
  
  METHODS
  Children aged 5-11 years old inhaled BDP 200 μg and formoterol 24 μg as fixed vs. free combination in an open label, randomized, two way crossover single dose study. Blood was collected pre-dose up to 8 h post-dose for pharmacokinetic evaluation (AUC(0,t), AUC(0,∞), AUC(0,0.5 h, Cmax , tmax , t1/2 ). Pharmacodynamics included heart rate, plasma potassium, urinary glucose and cortisol excretion. Peak expiratory flow and adverse events were monitored.
  
  
  RESULTS
  Twenty subjects were evaluable. The systemic exposure of B17MP and formoterol administered as fixed combination did not exceed the free combination: B17MP AUC(0,t) (pg ml(-1)  h) ratio test : reference (90% CI), 0.81 (0.697, 0.948) and formoterol AUC(0,t) (pg ml(-1)  h) ratio test : reference 0.97 (0.85, 1.10). All pharmacokinetic and pharmacodynamic end points showed non-superiority in favour of the test drug. One adverse event (vertigo) occurred but was not considered treatment-related.
  
  
  CONCLUSIONS
  BDP and formoterol pharmacokinetic and pharmacodynamic effects are non-superior after administration of the two actives as fixed vs. the free combination in 5-11-year-old asthmatic children.
authors.affiliation: Copenhagen University Hospital, Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Gentofte, Denmark.
authors.forename: Bo L K
authors.initials: BL
authors.lastname: Chawes
authors.forename: Annalisa
authors.initials: A
authors.lastname: Piccinno
authors.forename: Eskil
authors.initials: E
authors.lastname: Kreiner-Møller
authors.forename: Nadja H
authors.initials: NH
authors.lastname: Vissing
authors.forename: Porntiva
authors.initials: P
authors.lastname: Poorisrisak
authors.forename: Li
authors.initials: L
authors.lastname: Mortensen
authors.forename: Erik
authors.initials: E
authors.lastname: Nilson
authors.forename: Amalie
authors.initials: A
authors.lastname: Bisgaard
authors.forename: Anna
authors.initials: A
authors.lastname: Dossing
authors.forename: Maja
authors.initials: M
authors.lastname: Deleuran
authors.forename: Nanna L
authors.initials: NL
authors.lastname: Skytt
authors.forename: Nasim
authors.initials: N
authors.lastname: Samandari
authors.forename: Francesco
authors.initials: F
authors.lastname: Sergio
authors.forename: Giorgia
authors.initials: G
authors.lastname: Ciurlia
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Poli
authors.forename: Daniela
authors.initials: D
authors.lastname: Acerbi
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D000280:Administration, Inhalation; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001249:Asthma / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D001507:Beclomethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D000068759:Formoterol Fumarate; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D036501:Metered Dose Inhalers; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011188:Potassium / Q000097:blood
chemical_list: D018927:Anti-Asthmatic Agents; D004338:Drug Combinations; D004983:Ethanolamines; D005947:Glucose; D001507:Beclomethasone; D011188:Potassium; D000068759:Formoterol Fumarate; D006854:Hydrocortisone