Mode of action

Alvesco^® is administered as a prodrug, which is rapidly activated, mainly in the epithelial cells of the respiratory track and lungs.

Following inhalation, Alvesco^® is rapidly absorbed by the cells of the lung,¹ where it is converted into  activated desisobutyryl-ciclesonide (des-CIC).² Des-CIC has a high glucocorticoid receptor (GR) affinity³ and its influence on DNA transcription results in high anti-inflammatory activity, through activation of anti-inflammatory genes and downregulation of pro-inflammatory genes (Figure 1).

Des-CIC forms reversible lipid conjugates in the lung,⁴ creating a reservoir capable of releasing active metabolite and prolonging the anti-inflammatory effects of Alvesco^®. Together with high lipophilicity this allows for once-daily dosing.⁵ 

Figure 1: Mode of action of Alvesco^®

A new version of the Alvesco^{® m}ode of action video can be downloaded from here.

References:

1. 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
2. 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;73:1657-1664
3. 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;309:249-258
4. 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;18:390-396
5. Wilson AM, Duong M, Pratt B, et al. Anti-inflammatory effects of once daily low dose inhaled ciclesonide in mild to moderate asthmatic patients. Allergy 2006;61:537-542