title: Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent.
abstract: OBJECTIVE
  Prescription of inhaled corticosteroids to children with asthma is recommended at half the nominal dose of adults in order to reduce the risk of systemic side effects. However, there is a lack of pharmacokinetic trials supporting such dose reduction regimens. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed dose combination of beclometasone-dipropionate (BDP) and formoterol after dry powder inhaler (DPI) administration in children, adolescents and adults.
  
  
  METHODS
  The pharmacokinetic profiles of formoterol and beclometasone-17-monopropionate (B17MP; active metabolite of BDP) were evaluated over 8 h from two independent studies comprising children (6-11yrs, n = 27), adolescents (12-17 yrs, n = 28) and adults (≥18 yrs, n = 30) receiving a single, fixed dose of BDP/formoterol (children: 200 μg/24 μg, adolescents and adults: 400 μg/24 μg) via DPI.
  
  
  RESULTS
  The systemic exposure (AUC) for children versus adults was almost doubled for formoterol and similar for B17MP despite the halved BDP dose administered in children. In adolescents the AUC for formoterol and B17MP were approximately one third higher than in adults for both compounds. Upon normalization for the BDP/formoterol dose in the three populations the AUC and peak concentration (C(max)) correlated inversely with age and body surface area of the patients (r ≤ -0.53; p < 0.0001).
  
  
  CONCLUSIONS
  The systemic exposure to the active ingredients of BDP/formoterol administered as DPI correlates inversely with age and body size suggesting that dry powder dosage regimens should be adjusted for age and body size to avoid high systemic drug levels in children.
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. Electronic address: b_chawes@hotmail.com.
authors.forename: B L
authors.initials: BL
authors.lastname: Chawes
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Govoni
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Kreiner-Møller
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: N H
authors.initials: NH
authors.lastname: Vissing
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: P
authors.initials: P
authors.lastname: Poorisrisak
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Mortensen
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Nilsson
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Bisgaard
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Dossing
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Deleuran
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: N L
authors.initials: NL
authors.lastname: Skytt
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Samandari
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Piccinno
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Sergio
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ciurlia
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Poli
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici S.p.A., Parma, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Acerbi
authors.affiliation: University of Manchester, The Medicines Evaluation Unit, Manchester, United Kingdom.
authors.forename: D
authors.initials: D
authors.lastname: Singh
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Health Sciences, University of Copenhagen & Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Denmark. Electronic address: bisgaard@copsac.com.
authors.forename: H
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001507:Beclomethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049628:Body Size / Q000502:physiology; D002648:Child; D018592:Cross-Over Studies; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D006207:Half-Life; D006801:Humans; D036501:Metered Dose Inhalers; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D004983:Ethanolamines; D001507:Beclomethasone; D000068759:Formoterol Fumarate
keywords: Adolescents; Asthma; Beclometasone-dipropionate; Children; DPI; Formoterol