Deposition and metabolism of inhaled ciclesonide in the human lung

作者：Nave R^*; Watz H; Hoffmann H; Boss H; Magnussen H

来源：European Respiratory Journal, 2010, 36(5): 1113-1119.

DOI：10.1183/09031936.00172309

• Ciclesonide
• human
• in vivo
• lung metabolism

Ciclesonide is an inhaled corticosteroid, administered as a prodrug via a metered-dose inhaler. Following deposition in the lung, ciclesonide is hydrolysed by esterases to form the pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC). Formation of des-CIC, as well as reversible esterification of des-CIC with fatty acids, has been demonstrated in vitro. The aim of this study was to investigate the in vivo metabolism of ciclesonide in the human lung.
This single-dose, open-label, nonrandomised study was performed in 20 patients undergoing planned lung surgery for treatment of malignant pulmonary lesions. Patients inhaled a single dose of 1,280 mu g ciclesonide at various time-points between 2 and 24 h prior to lung tissue resection. The concentration of ciclesonide, des-CIC and fatty acid conjugates of des-CIC in tissue samples was determined. Serum samples for pharmacokinetic analysis were taken at several time-points after inhalation.
The pharmacokinetics in serum indicated that the inhalation by the patients was adequate. Metabolites (des-CIC, des-CIC oleate and des-CIC palmitate) were detected in the resected central and peripheral lung tissues. A substantial portion of ciclesonide was already activated to des-CIC at the first time-point of tissue analysis.
Activation of ciclesonide and formation of des-CIC fatty acid conjugates was confirmed in vivo in the human lung.

• 出版日期2010-11