Alvesco

Specific pharmacology

Alvesco® is an inhaled corticosteroid (ICS) with specific pharmacology, which can help optimize the treatment of asthma (Figure 1). The specific properties of Alvesco®, which contribute to its efficacy and tolerability profiles, are illustrated below.

21 fig 1Cinammon man specific pharmacology
Figure 1: Alvesco® has a specific pharmacological profile

  • Administered as a prodrug, Alvesco® exhibits a high total lung deposition of 52%, of which 55% is distributed to the small airways,1 and low oropharyngeal deposition.2 
  • Alvesco® is highly lipophilic and is absorbed quickly by lung epithelial cells,3 where it is converted to the active metabolite desisobutyryl-ciclesonide (des-CIC),4 which reduces inflammation.
  • Alvesco® has a low oral bioavailability due to high first pass metabolism.5 
  • The small particle size of Alvesco® enables it to enter the small airways,1,10 where it may improve small airway function.11,12 Alvesco® has also been shown to improve measures of large airway function.13 
  • Des-CIC forms reversible lipid conjugates in the lung, creating a reservoir capable of releasing active metabolite and prolonging the anti-inflammatory effects of Alvesco®. This allows for once-daily-dosing.8
  • The low availability of Alvesco® outside the lungs, along with rapid clearance of the drug and high protein-binding, limit the systemic activity of Alvesco®.5,7,9,14

References
  1. 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;100:375-84.
  2. Richter K, Kanniess F, Biberger C, et al. Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma. J Clin Pharmacol 2005;45:146-52.
  3. Nonaka T, Nave R, McCracken N, et al. Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549). BMC Pharmacol 2007;7:12.
  4. Mutch E, Nave R, McCracken N, et al. The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol 2007;73:1657-64.
  5. Nave R, Bethke TD, van Marle SP, Zech K. Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects. Clin Pharmacokinet 2004;43:479-86.
  6. Stoeck M, Riedel R, Hochhaus G, et al. In vitro and in vivo anti-inflammatory activity of the new glucocorticoid ciclesonide. J Pharmacol Exp Ther 2004;309:249-58.
  7. Rohatagi S, Luo Y, Shen L, et al. Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide. Am J Ther 2005;12:201-9.
  8. Nave R, Meyer W, Fuhst R, et al. Formation of fatty acid conjugates of ciclesonide active metabolite in the rat lung after 4 week inhalation of ciclesonide. Pulm Pharmacol Ther 2005;18:390-6.
  9. Alvesco® EU SmPC. Date of last revision: November 2012.
  10. 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 2006;19(2):117-26.
  11. Cohen J, Douma WR, ten Hacken NH, et al. Ciclesonide improves measures of small airway involvement in asthma. Eur Respir J 2008;31:1213-20.
  12. Hoshino M. Comparison of effectiveness in ciclesonide and fluticasone propionate on small airway function in mild asthma. Allergol Int 2010;59:59-66.
  13. Vogelmeier CF, Hering T, Lewin T, et al. Efficacy and safety of ciclesonide in the treatment of 24,037 asthmatic patients in routine medical care. Respir Med 2011;105:186-94.
  14. 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;18:328-36.
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