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Lower oropharyngeal deposition of inhaled ciclesonide via hydrofluoroalkane metered-dose inhaler compared with budesonide via chlorofluorocarbon metered-dose inhaler in healthy subjects

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

Inhaled corticosteroids may cause oropharyngeal side effects if deposited in the oropharynx in active form. Ciclesonide, an inhaled corticosteroid with low glucocorticoid receptor affinity, is activated primarily in the lung by esterases to an active metabolite, desisobutyryl-ciclesonide (des-CIC), with high glucocorticoid receptor affinity. We studied oropharyngeal deposition of ciclesonide, des-CIC, and budesonide.

Methods

In an open-label, randomized, two-treatment (administered in sequence), five-period study, 18 healthy subjects received 800 μg (ex-valve) inhaled ciclesonide via a hydrofluoroalkane-pressurized, metered-dose inhaler followed by 800 μg budesonide (Pulmicort) by a chlorofluorocarbon-pressurized, metered-dose inhaler (four puffs of 200 μg each, ex-valve) or vice versa. Oropharyngeal cavity rinsing was performed immediately, or 15, 30, 45, or 60 min after inhalation (one rinsing per study period), and the solutions were analyzed using liquid chromatography with tandem mass spectrometric detection.

Results

Ciclesonide and budesonide were detected in most oropharyngeal wash samples. Maximal concentration of each inhaled corticosteroid was reached immediately post-inhalation; maximal concentrations of ciclesonide and des-CIC were 30% and 0.67%, respectively, of budesonide. Oropharyngeal deposition of ciclesonide and budesonide decreased rapidly within 15 min post-inhalation, and less rapidly thereafter. Less than 10% of the residual ciclesonide in the oropharynx was converted to des-CIC. The molar dose-adjusted amount of des-CIC was 4% of budesonide (P < 0.0001). There were no significant adverse events.

Conclusion

Oropharyngeal deposition of des-CIC was more than one order of magnitude lower than that of budesonide when administered by the respective metered-dose inhalers. This may explain the low frequency of oropharyngeal side effects of ciclesonide in clinical studies.

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Acknowledgements

The following investigators participated in this study: Manfred Hartmann, MD, MSc, Bernhard Hauns, MD, Ulrich Kilian, MD, and Wolfgang Timmer, MD. The authors would like to thank Mr. Werner Meyer (MDS Pharmaservices, Fehraltorf, Switzerland) for performing the bioanalytical work.

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

    Ruediger Nave, Karl Zech & Thomas D. Bethke

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  1. Ruediger Nave
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  2. Karl Zech
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  3. Thomas D. Bethke
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Correspondence to Ruediger Nave.

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Nave, R., Zech, K. & Bethke, T.D. Lower oropharyngeal deposition of inhaled ciclesonide via hydrofluoroalkane metered-dose inhaler compared with budesonide via chlorofluorocarbon metered-dose inhaler in healthy subjects. Eur J Clin Pharmacol 61, 203–208 (2005). https://doi.org/10.1007/s00228-005-0910-0

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  • DOI: https://doi.org/10.1007/s00228-005-0910-0

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