Abstract
Introduction: Inhaled glucocorticoids (IGCS) have become the first-line therapy of asthma. By increasing the retention time of IGCS in the airway-lung tissue, it might be possible to prolong the interval between doses, thus increasing the compliance to the therapy. The retention of IGCS in the airway epithelium has been correlated to its non-specific binding to cellular and subcellular membranes (related to the lipophilicity of drugs). Recent studies have evaluated the clinical efficacy of IGCS using a same total dose given once or twice daily. It has been reported that Budesonide (Bude) given once daily is as effective as the same total dose given twice daily in the therapy of mild-moderate asthma. Contrarily, the efficacy of other more lipophilic IGCS has been shown to be different when comparing both inhalation regimens. In vivo and in vitro experiments have demonstrated that Bude is accumulated within airway tissue due to the formation of inactive pharmacological esters. Objectives: To evaluate the uptake, accumulation, and eventual release of Bude in a human bronchial cell line in vitro (Calu-3 cell in monolayers). Material and Methods: Monolayers of Calu-3 cells were cultured. Each monolayer was placed between two sample compartments, an apical and a basolateral chamber. Bude solution was applied on the apical chamber for 2 hr. To evaluate the release of Bude accumulated within the cells, both chambers were washed with free-Bude solution. Appearance of the drug in the chambers was followed for 12 hrs. In order to assess if Bude was accumulated in the cells, lysis of the monolayers was performed followed by Mass Spectrometry identificaton of Bude and its esters. Results: Bude was efficiently taken up by the cells and a substantial fraction remained within the cells, mainly as derivative compounds. Bude was then released only as its active form due to the reversibility of the esterification. The release of Budes continued at least during the following 12 hrs. These observations in Calu-3 cells monolayers complement previous results on the efficacy of Bude by once daily inhalation.
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Cassara, M., Figueroa, J., Roemele, P. et al. Uptake, Accumulation and Release of Budesonide in an In Vitro Model of Human Bronchial Cells (Calu-3) Cultured in Monolayers. Pediatr Res 53, 869 (2003). https://doi.org/10.1203/00006450-200305000-00032
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DOI: https://doi.org/10.1203/00006450-200305000-00032