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Pharmacokinetic and Pharmacodynamic Properties of Inhaled Ciclesonide

From the Department of Pharmaceutics, University of Florida, Gainesville.

Inhaled corticosteroids are recommended first-line therapy for persistent asthma of all severities; however, oropharyngeal and systemic adverse events can be a concern. Inhaled corticosteroids exert their therapeutic and adverse effects by interacting with glucocorticoid receptors within and outside the lungs, respectively. Ciclesonide is a novel inhaled corticosteroid that possesses a unique pharmacokinetic and pharmacodynamic profile. Ciclesonide is inactive itself and converted to its pharmacologically active metabolite, desisobutyryl-ciclesonide, in the target organ, the lungs. Pulmonary activation combined with low oral deposition may minimize oropharyngeal adverse events, and low oral bioavailability, rapid clearance, and high protein binding may reduce systemic exposure. In addition, high pulmonary deposition due to the highly respirable particles, combined with the potential for prolonged lung retention via lipid conjugation, provides for effective therapeutic action.

Key Words: Ciclesonide • inhaled corticosteroids • safety • pharmacokinetic • pharmacodynamic

Address for reprints: Hartmut Derendorf, PhD, FCP, Department of Pharmaceutics, University of Florida, Gainesville, FL 32610; e-mail: hartmut{at}cop.ufl.edu.