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Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)

BACKGROUND: Ciclesonide is a novel inhaled corticosteroid for the treatment of airway inflammation. In this study we investigated uptake and in vitro metabolism of ciclesonide in human alveolar type II epithelial cells (A549). Ciclesonide uptake was compared with fluticasone propionate, an inhaled c...

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Autores principales: Nonaka, Takashi, Nave, Rüdiger, McCracken, Nigel, Kawashimo, Atsuko, Katsuura, Yasuhiro
Formato: Texto
Lenguaje:English
Publicado: BioMed Central|1 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048954/
https://www.ncbi.nlm.nih.gov/pubmed/17900334
http://dx.doi.org/10.1186/1471-2210-7-12
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author Nonaka, Takashi
Nave, Rüdiger
McCracken, Nigel
Kawashimo, Atsuko
Katsuura, Yasuhiro
author_facet Nonaka, Takashi
Nave, Rüdiger
McCracken, Nigel
Kawashimo, Atsuko
Katsuura, Yasuhiro
author_sort Nonaka, Takashi
collection PubMed
description BACKGROUND: Ciclesonide is a novel inhaled corticosteroid for the treatment of airway inflammation. In this study we investigated uptake and in vitro metabolism of ciclesonide in human alveolar type II epithelial cells (A549). Ciclesonide uptake was compared with fluticasone propionate, an inhaled corticosteroid that is not metabolized in lung tissue. A549 cells were incubated with 2 × 10(-8 )M ciclesonide or fluticasone propionate for 3 to 30 min to determine uptake; or with 2 × 10(-8 )M ciclesonide for 1 h, followed by incubation with drug-free buffer for 3, 6, and 24 h to analyze in vitro metabolism. High performance liquid chromatography with tandem mass spectrometry was used to measure the concentrations of both corticosteroids and metabolites. RESULTS: At all time points the mean intracellular concentration was higher for ciclesonide when compared with fluticasone propionate. Activation of ciclesonide to desisobutyryl-ciclesonide (des-CIC) was confirmed and conjugates of des-CIC with fatty acids were detected. The intracellular concentration of ciclesonide decreased over time, whereas the concentration of des-CIC remained relatively stable: 2.27 to 3.19 pmol/dish between 3 and 24 h. The concentration of des-CIC fatty acid conjugates increased over time, with des-CIC-oleate being the main metabolite. CONCLUSION: Uptake of ciclesonide into A549 cells was more efficient than that of the less lipophilic fluticasone propionate. Intracellular concentrations of the pharmacologically active metabolite des-CIC were maintained for up to 24 h. The local anti-inflammatory activity of ciclesonide in the lung may be prolonged by the slow release of active drug from the depot of fatty acid esters.
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spelling pubmed-20489542007-11-03 Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549) Nonaka, Takashi Nave, Rüdiger McCracken, Nigel Kawashimo, Atsuko Katsuura, Yasuhiro BMC Pharmacol Research Article BACKGROUND: Ciclesonide is a novel inhaled corticosteroid for the treatment of airway inflammation. In this study we investigated uptake and in vitro metabolism of ciclesonide in human alveolar type II epithelial cells (A549). Ciclesonide uptake was compared with fluticasone propionate, an inhaled corticosteroid that is not metabolized in lung tissue. A549 cells were incubated with 2 × 10(-8 )M ciclesonide or fluticasone propionate for 3 to 30 min to determine uptake; or with 2 × 10(-8 )M ciclesonide for 1 h, followed by incubation with drug-free buffer for 3, 6, and 24 h to analyze in vitro metabolism. High performance liquid chromatography with tandem mass spectrometry was used to measure the concentrations of both corticosteroids and metabolites. RESULTS: At all time points the mean intracellular concentration was higher for ciclesonide when compared with fluticasone propionate. Activation of ciclesonide to desisobutyryl-ciclesonide (des-CIC) was confirmed and conjugates of des-CIC with fatty acids were detected. The intracellular concentration of ciclesonide decreased over time, whereas the concentration of des-CIC remained relatively stable: 2.27 to 3.19 pmol/dish between 3 and 24 h. The concentration of des-CIC fatty acid conjugates increased over time, with des-CIC-oleate being the main metabolite. CONCLUSION: Uptake of ciclesonide into A549 cells was more efficient than that of the less lipophilic fluticasone propionate. Intracellular concentrations of the pharmacologically active metabolite des-CIC were maintained for up to 24 h. The local anti-inflammatory activity of ciclesonide in the lung may be prolonged by the slow release of active drug from the depot of fatty acid esters. BioMed Central|1 2007-09-27 /pmc/articles/PMC2048954/ /pubmed/17900334 http://dx.doi.org/10.1186/1471-2210-7-12 Text en Copyright © 2007 Nonaka et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Nonaka, Takashi
Nave, Rüdiger
McCracken, Nigel
Kawashimo, Atsuko
Katsuura, Yasuhiro
Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)
title Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)
title_full Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)
title_fullStr Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)
title_full_unstemmed Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)
title_short Ciclesonide uptake and metabolism in human alveolar type II epithelial cells (A549)
title_sort ciclesonide uptake and metabolism in human alveolar type ii epithelial cells (a549)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048954/
https://www.ncbi.nlm.nih.gov/pubmed/17900334
http://dx.doi.org/10.1186/1471-2210-7-12
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