title: Equivalent pharmacokinetics of the active metabolite of ciclesonide with and without use of the AeroChamber Plus spacer for inhalation.
abstract: BACKGROUND
  Ciclesonide is an inhaled corticosteroid that provides safe and effective control of persistent asthma. Ciclesonide is administered as an aerosol solution in a metered-dose inhaler, using hydrofluoroalkane-134a as a propellant. It is activated in the lung to form its only active metabolite, desisobutyryl-ciclesonide (des-CIC). A spacer may be used in combination with the hydrofluoroalkane metered-dose inhaler (HFA-MDI) to maintain inhaled corticosteroid delivery to the lung in patients with poor inhalation technique.
  
  
  OBJECTIVE
  To determine if the pharmacokinetics of des-CIC and ciclesonide are altered when a spacer is used for ciclesonide inhalation.
  
  
  METHODS
  A randomised, open-label, 2-period crossover, single-center pharmacokinetic study was conducted in 30 patients with asthma (forced expiratory volume in 1 second > or = 70% predicted). A single dose of ciclesonide (320 microg ex-actuator; equivalent to 400 microg ex-valve) was administered via the HFA-MDI with and without an AeroChamber Plus spacer (Trudell Medical International, London, ON, Canada). Serum concentrations of ciclesonide and des-CIC were measured before inhalation and at various intervals until 14 hours after treatment using high-performance liquid chromatography with tandem mass spectrometric detection.
  
  
  RESULTS
  The pharmacokinetic properties of the active metabolite, des-CIC, were equivalent after inhalation of ciclesonide with and without the AeroChamber Plus spacer. Point estimates and 90% confidence intervals (CIs) for the ratio of des-CIC pharmacokinetic properties in the presence or absence of a spacer were within the conventional bioequivalence range of 0.80-1.25 (area under the serum concentration time curve from time zero to infinity 0.96 [0.85, 1.07]; peak serum concentration 1.05 [0.94, 1.18]; elimination half-life 1.04 [0.92, 1.18]). Furthermore, there was no relevant difference in the point estimate and 90% CI of the difference of the time to reach peak serum concentration of des-CIC with or without a spacer.
  
  
  CONCLUSIONS
  The AeroChamber Plus spacer did not influence the pharmacokinetics of the pharmacologically active des-CIC. Thus, systemic exposure to the active metabolite is similar when ciclesonide is inhaled with or without a spacer. Furthermore, these results are indicative of comparable lung deposition of ciclesonide in both the presence and absence of a spacer.
authors.affiliation: ALTANA Pharma AG, Konstanz, Germany. anton.drollmann@atlantapharma.com
authors.forename: Anton
authors.initials: A
authors.lastname: Drollmann
authors.forename: Ruediger
authors.initials: R
authors.lastname: Nave
authors.forename: Volker W
authors.initials: VW
authors.lastname: Steinijans
authors.forename: Eugen
authors.initials: E
authors.lastname: Baumgärtner
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bethke
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D011282:Pregnenediones / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide