Deposition and metabolism of inhaled ciclesonide in the human lung
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 es...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 31, 2010
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| In: |
The European respiratory journal
Year: 2010, Volume: 36, Issue: 5, Pages: 1113-1119 |
| ISSN: | 1399-3003 |
| DOI: | 10.1183/09031936.00172309 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1183/09031936.00172309 Verlag, lizenzpflichtig, Volltext: https://erj.ersjournals.com/content/36/5/1113 
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| Author Notes: | R. Nave, H. Watz, H. Hoffmann, H. Boss and H. Magnussen |
MARC
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| 520 | |a 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 μg 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. | ||
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