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
The use of trade names is for product identification purposes only and does not imply endorsement.
References
Georgitis JW. The 1997 Asthma Management Guidelines and therapeutic issues relating to the treatment of asthma. Chest 1999 Jan; 115(1): 210–7
Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: a systematic review and meta-analysis. Arch Intern Med 1999 May; 159(9): 941–55
Jackson LD, Polygenis D, McIvor RA, et al. Comparative efficacy and safety of inhaled corticosteroids in asthma. Can J Clin Pharmacol 1999 Spring; 6(1): 26–37
Leach CL, Davidson PJ, Boudreau RJ. Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone. Eur Respir J 1998 Dec; 12(6): 1346–53
Cave A, Arlett P, Lee E. Inhaled and nasal corticosteroids: factors affecting the risks of systemic adverse effects. Pharmacol Ther 1999 Sep; 83(3): 153–79
Konig P. Spacer devices used with metered-dose inhalers: breakthrough or gimmick? Chest 1985 Aug; 88(2): 276–84
Newman S, Salmon A, Nave R, et al. High lung deposition of 99mTc-labeled ciclesonide administered via HFA-MDI to patients with asthma. Respir Med 2006; 100(3): 375–84
Mutch E, Nave R, Zech K, et al. Esterases involved in the hydrolysis of ciclesonide in human tissues [abstract]. Eur Respir J 2003; 22 (45 Suppl.) 1749
Nave R, Fisher R, Zech K. In vitro metabolism of ciclesonide in human lung and liver precision-cut tissue slices. Biopharm Drug Dispos 2006; 27(4): 197–207
Ukena D, Biberger C, von Behren V, et al. Ciclesonide significantly improves pulmonary function when compared with budesonide: a randomized 12-week study [abstract no. P2640]. Eur Respir J 2003 Sep; 22 Suppl. 45: 411s
Buhl R, Vinkler I, Magyar P, et al. Comparable efficacy of ciclesonide once daily versus fluticasone propionate twice daily in asthma. Pulm Pharmacol Ther. 2005 Nov 23, [Epub ahead of print]
Lipworth BJ, Kaliner MA, LaForce CF, et al. Effect of ciclesonide and fluticasone on hypothalamic-pituitary-adrenal axis function in adults with mild-to-moderate persistent asthma. Ann Allergy Asthma Immunol 2005 Apr; 94(4): 465–72
Derom E, Van De Velde V, Marissens S, et al. Effects of inhaled ciclesonide and fluticasone propionate on cortisol secretion and airway responsiveness to adenosine 5’monophosphate in asthmatic patients. Pulm Pharmacol Ther 2005; 18(5): 328–36
Nave R, Zech K, Bethke TD. 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 2005 May; 61(3): 203–8
European Pharmacopoeia, 5th edition online. Section 2.9.18 Preparations for inhalations: aerodynamic assessment of fine particles 04-2005: 20918; Apparatus D - Andersen Cascade Impactor [online]. Available from URL: http://online.pheur.org [Accessed 2005 Jun 23]
Spacers and holding chambers for use with metered-dose inhalers [standard]. Publication Z264.1-02. Mississauga (ON): Canadian Standards Association, 2002 Oct
Sauter R, Steinijans VW, Diletti E, et al. Presentation of results from bioequivalence studies. Int J Clin Pharmacol Ther Toxicol 1992 Jul; 30(7): 233–56
Chapman KR, Patel P, D’Urzo AD, et al. Maintenance of asthma control by once-daily inhaled ciclesonide in adults with persistent asthma. Allergy 2005; 60(3): 330–7
Postma DS, Sevette C, Martinat Y, et al. Treatment of asthma by the inhaled corticosteroid ciclesonide given either in the morning or evening. Eur Respir J 2001 Jun; 17: 1083–8
Stoeck M, Riedel R, Hochhaus G, et al. In vitro and in vivo antiinflammatory activity of the new glucocorticoid ciclesonide. J Pharmacol Exp Ther 2004 Apr; 309(1): 249–58
Nave R, Bethke TD, van Marie SP, et al. Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet 2004; 43(7): 479–86
Peet CF, Enos T, Nave R, et al. Identification of enzymes involved in phase I metabolism of ciclesonide by human liver microsomes. Eur J Drug Metab Pharmacokinet 2005 Oct-Dec; 30(4): 275–86
Leach CL, Bethke TD, Boudreau RJ, et al. 2-D and 3-D imaging show ciclesonide has high lung deposition and peripheral distribution: a nonrandomized study in healthy volunteers. J Aerosol Med. In press.
Leach CL, Davidson PJ, Hasselquist BE, et al. Lung deposition of hydrofluoroalkane-134abeclomethasone is greater than that of chlorofluorocarbon fluticasone and chlorofluorocarbon beclomethasone: a cross-over study in healthy volunteers. Chest 2002 Aug; 122(2): 510–6
Pickering H, Pitcairn GR, Hirst PH, et al. Regional lung deposition of a technetium 99m-labeled formulation of mometasone furoate administered by hydrofluoroalkane 227 metered-dose inhaler. Clin Ther 2000 Dec; 22(12): 1483–93
Thorsson L, Edsbacker S, Conradson TB. Lung deposition of budesonide from Turbuhaler is twice that from a pressurized metered-dose inhaler P-MDI. Eur Respir J 1994 Oct; 7(10): 1839–44
Nelson HS, Loffert DT. Comparison of the bronchodilator response to albuterol administered by the OptiHaler, the AeroChamber, or by metered dose inhaler alone. Ann Allergy 1994 Apr; 72(4): 337–40
Cheng NG, Browne GJ, Lam LT, et al. Spacer compliance after discharge following a mild to moderate asthma attack. Arch Dis Child 2002 Oct; 87(4): 302–5
Pedersen S, Frost L, Arnfred T. Errors in inhalation technique and efficiency in inhaler use in asthmatic children. Allergy 1986 Feb; 41(2): 118–24
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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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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DOI: https://doi.org/10.2165/00003088-200645070-00007