Clinical pharmacokinetic and pharmacodynamic profile of inhaled ciclesonide.
Asthma is a chronic inflammatory disease of the airways, and inhaled corticosteroids (ICSs) are recommended as first-line therapy for persistent asthma of all severities. Ciclesonide is a novel ICS, which is administered as an aerosol solution in a metered-dose inhaler, using hydrofluoroalkane-134a as a propellant. Because of the high respirable particle fraction, high pulmonary deposition is obtained in patients, which constitutes the basis of effective therapeutic action. The parent compound, ciclesonide, is pharmacologically inactive and is activated in the target organ, the lung, to form its only pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC). Low oral deposition combined with minimal formation of des-CIC in the oropharynx may minimize the typical oropharyngeal adverse events associated with ICSs. Low oral bioavailability, rapid clearance and high protein binding reduce pharmacologically relevant systemic exposure. The unique pharmacokinetic and pharmacodynamic profile of ciclesonide offers a rationale that supports the favourable risk-benefit profile observed in clinical trials in patients with persistent asthma.
Nave
Rüdiger
R
Department of Pharmacometrics/Pharmacokinetics, Nycomed GmbH, Konstanz, Germany. ruediger.nave@nycomed.com
D000280:Administration, Inhalation; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy*; D004347:Drug Interactions; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D015394:Molecular Structure; D009960:Oropharynx / Q000378:metabolism; D011282:Pregnenediones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011485:Protein Binding; D011877:Radionuclide Imaging
D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; C494355:desisobutyrylciclesonide; C120481:ciclesonide