Equivalent pharmacokinetics of the active metabolite of ciclesonide with and without use of the AeroChamber Plus spacer for inhalation.
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.
Drollmann
Anton
A
ALTANA Pharma AG, Konstanz, Germany. anton.drollmann@atlantapharma.com
Nave
Ruediger
R
Steinijans
Volker W
VW
Baumgärtner
Eugen
E
Bethke
Thomas D
TD
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
D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide