title: The systemic exposure to inhaled beclometasone/formoterol pMDI with valved holding chamber is independent of age and body size.
abstract: BACKGROUND
  Asthma guidelines recommend prescription of inhaled corticosteroids at a reduced dosage in children compared to older patients in order to minimize the systemic exposure and risk of unwanted side effects. In children, pressurized metered dose inhalers (pMDI) are recommended in combination with a valved holding chamber (VHC) to overcome the problem of coordinating inhalation with actuation. However, the influence of age and body size on the systemic exposure of drugs to be administered via a pMDI with VHC is still not fully elucidated. Therefore, we aimed to compare the systemic exposure to the active ingredients of a fixed combination of beclometasone-dipropionate/formoterol-fumarate administered via pMDI with VHC in children, adolescents and adults.
  
  
  METHODS
  The pharmacokinetics of formoterol and beclometasone-17-monopropionate (active metabolite of beclometasone-dipropionate) was evaluated over 8 h from three studies, each performed in a different age and body size group. Children (7-11 years, n = 20), adolescents (12-17 years, n = 29) and adults (≥18 years, n = 24) received a single dose of beclometasone/formoterol (children: 200 μg/24 μg, adolescents and adults: 400 μg/24 μg) via pMDI with AeroChamber Plus™.
  
  
  RESULTS
  The systemic exposure in children in comparison to adolescents was equivalent for formoterol while it was halved for beclometasone-17-monopropionate in accordance with the halved dose of beclometasone administered in children (90% CIs within 0.8-1.25 for formoterol and 0.4-0.625 for beclometasone-17-monopropionate). The systemic exposure to beclometasone-17-monopropionate and formoterol was equivalent between adolescents and adults.
  
  
  CONCLUSIONS
  The systemic exposure to the active ingredients of a fixed dose combination of beclometasone/formoterol administered via pMDI with AeroChamber Plus™ correlates with the nominal dose independently of patient age and body size. Thus, dose reduction in relation to age when using a pMDI with VHC may be unnecessary for reducing the systemic exposure in children.
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici, Parma 43122, Italy. Electronic address: m.govoni@chiesi.com.
authors.forename: Mirco
authors.initials: M
authors.lastname: Govoni
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici, Parma 43122, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Piccinno
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici, Parma 43122, Italy.
authors.forename: Germano
authors.initials: G
authors.lastname: Lucci
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici, Parma 43122, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Poli
authors.affiliation: Department of Clinical Pharmacology, Chiesi Farmaceutici, Parma 43122, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Acerbi
authors.affiliation: Department of Statistics and Data Management, Chiesi Farmaceutici, Parma 43122, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Baronio
authors.affiliation: University of Manchester, The Medicines Evaluation Unit, Manchester M23 9QZ, United Kingdom.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, 90-153, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuna
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: Bo L K
authors.initials: BL
authors.lastname: Chawes
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: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018927:Anti-Asthmatic Agents; D004338:Drug Combinations; D004983:Ethanolamines; D001507:Beclomethasone; D000068759:Formoterol Fumarate
keywords: Adolescents; Adults; Asthma; Beclometasone; Children; Formoterol