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Equivalent Pharmacokinetics of the Active Metabolite of Ciclesonide With and Without Use of the AeroChamber Plus™ Spacer for Inhalation

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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 pharma-cokinetic study was conducted in 30 patients with asthma (forced expiratory volume in 1 second ≥70% predicted). A single dose of ciclesonide (320μg exactuator; equivalent to 400μg 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.

Conclusion

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.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

We would like to thank Dr Günter Stingel and Dr Helgert Müller, ALTANA Pharma AG, for providing assistance in this study. We would also like to thank Mr Werner Meyer, MDS Pharma Services, Switzerland, for performing the bioanalytical work.

This study was sponsored by ALTANA Pharma AG, Konstanz, Germany. The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. ALTANA Pharma AG, Byk-Gulden-Str. 2, Konstanz, 78467, Germany

    Anton Drollmann, Ruediger Nave, Volker W. Steinijans & Thomas D. Bethke

  2. Quintiles GmbH, Freiburg, Germany

    Eugen Baumgärtner

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  1. Anton Drollmann
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  2. Ruediger Nave
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  3. Volker W. Steinijans
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  4. Eugen Baumgärtner
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  5. Thomas D. Bethke
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Correspondence to Anton Drollmann.

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Drollmann, A., Nave, R., Steinijans, V.W. et al. Equivalent Pharmacokinetics of the Active Metabolite of Ciclesonide With and Without Use of the AeroChamber Plus™ Spacer for Inhalation. Clin Pharmacokinet 45, 729–736 (2006). https://doi.org/10.2165/00003088-200645070-00007

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