title: Similar Results in Children with Asthma for Steady State Pharmacokinetic Parameters of Ciclesonide Inhaled with or without Spacer.
abstract: BACKGROUND
  Ciclesonide is an inhaled corticosteroid administered by a metered dose inhaler (MDI) to treat bronchial asthma. After inhalation, the inactive ciclesonide is converted by esterases in the airways to active metabolite desisobutyryl-ciclesonide (des-CIC).
  
  
  OBJECTIVE
  To compare the pharmacokinetic (PK) parameters of des-CIC in children after administration of therapeutic dose of ciclesonide with and without spacer (AeroChamber Plus(™)).
  
  
  METHODS
  Open-label, 3 period, cross over, repeated dose, PK study in 37 children with mild to moderate stable asthma (age: 6-11 y; body weight: 20-53 kg). During each 7-day treatment period, ciclesonide was inhaled once in the morning: A) 160 μg MDI with spacer, B) 80 μg MDI with spacer, and C) 160 μg MDI without spacer. Serum PK parameters of ciclesonide and des-CIC were determined on Day 7 of each period. The primary PK parameters were the AUCτ and Cmax for des-CIC.
  
  
  RESULTS
  Inhaling ciclesonide with spacer led to a dose proportional systemic exposure (AUCτ) of des-CIC (0.316 μg*h/L for 80 μg and 0.663 μg*h/L for 160 μg). The dose-normalized systemic exposure for des-CIC (based on AUCτ) was 27% higher after inhalation of ciclesonide 80 μg or 160 μg with spacer than without spacer; the corresponding Cmax values for des-CIC were, respectively, 63% and 55% higher with spacer. No clinically relevant abnormalities or adverse drug reactions were observed.
  
  
  CONCLUSIONS
  Inhalation of therapeutic ciclesonide dose with spacer led to a slight increase in the systemic exposure of des-CIC, which does not warrant dose adjustment.
authors.affiliation: Nycomed GmbH, Byk Gulden Str. 2, 78467 Konstanz, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Boss
authors.forename: P
authors.initials: P
authors.lastname: Minic
authors.forename: R
authors.initials: R
authors.lastname: Nave
keywords: asthma; children; ciclesonide; pharmacokinetics; spacer