SELECTED ARTICLES FROM THE RECENT LITERATURE 2006

11/13/06

Ciclesonide treatment of asthma

Summary
Background - Major attempts have been made to develop inhaled corticosteroid (ICS) agents with less potential for adverse effects during the treatment of persistent asthma.

Findings - Colice of the Washington Hospital Center in Washington, DC reviewed characteristics of ciclesonide (Cic) a recently developed ICS agent. Cic is formulated as an aerosol placed within a MDI with a HFA propellant. The mass median particle diameter of Cic is 1-2 microns providing excellent drug deposition within the lower airways. Cic exists as a non-active prodrug which undergoes reversible esterification in the lungs, possibly allowing once daily dosing. A metabolite of Cic with corticosteroid activity on asthmatic inflammation is formed in the lower airways. Once the Cic metabolite is absorbed from the lungs into the systemic circulation, it is it is almost completely bound to plasma proteins leaving very little free metabolite to bind to corticosteroid receptors on systemic tissues. As a result, there are reduced systemic corticosteroid effects.

These findings likely explain the clinical efficacy of Cic treatment in asthma with a very favorable safety profile.

Reference
Expert Opin Pharmacother 2006;7:2107-17

Editor's Comments
The very favorable safety profile of Cic appears to be related to the almost 100% binding of absorbed Cic metabolite to plasma proteins, essentially preventing binding of Cic metabolite to receptors on systemic tissues. Once bound to plasma proteins the Cic metabolite is rapidly disposed of and excreted. Another advantage of Cic treatment is that there is a very low incidence of pharyngeal adverse effects because the inhaled Cic has no corticosteroid effects until it is converted into an active metabolite in the lower airways.

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