Document Detail


Reversible formation of fatty acid esters of budesonide, an antiasthma glucocorticoid, in human lung and liver microsomes.
MedLine Citation:
PMID:  9351909     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microsomes from human lung and liver catalyze the formation of fatty acid esters of budesonide, a glucocorticoid used for inhalation treatment of asthma. The conjugation was dependent on coenzyme A and ATP. Addition of free fatty acids to the incubations affected the pattern of metabolites, but ester formation was observed also without such addition. Budesonide oleate, palmitate, linoleate, palmitoleate, and arachidonate were identified as metabolites. The fatty acid conjugates of budesonide were shown to be substrates for lipase in vitro, thus budesonide is regainable from the conjugates. The data suggest that an equilibrium between budesonide and these pharmacologically inactive lipoidal conjugates will be established in tissues at repeated exposure to budesonide. Since the fatty acid conjugates most likely will be retained intracellularly for a longer time than unchanged budesonide, the duration of tissue exposure to budesonide will depend partly on the rate of lipase-catalyzed hydrolysis of the conjugates. The findings in this study provide a possible explanation for the efficacy of budesonide in mild asthmatics also when inhaled once daily.
Authors:
A Tunek; K Sjödin; G Hallström
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  25     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1998-02-09     Completed Date:  1998-02-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1311-7     Citation Subset:  IM    
Affiliation:
Preclinical Research and Development, Astra Draco AB.
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MeSH Terms
Descriptor/Qualifier:
Anti-Asthmatic Agents / pharmacokinetics*
Budesonide / pharmacokinetics*
Chromatography, Liquid
Esters / chemistry,  metabolism
Fatty Acids / chemistry,  metabolism*
Humans
Hydrolysis
Lipase / chemistry
Lung / metabolism*,  ultrastructure
Mass Spectrometry
Microsomes / metabolism*
Microsomes, Liver / metabolism*
Chemical
Reg. No./Substance:
0/Anti-Asthmatic Agents; 0/Esters; 0/Fatty Acids; 51333-22-3/Budesonide; EC 3.1.1.3/Lipase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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