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    
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.
A Tunek; K Sjödin; G Hallström
Related Documents :
176359 - Adriamycin analogs. periodate oxidation of adriamycin.
3827909 - Nonoxidative ethanol metabolism in human leukocytes: detection of fatty acid ethyl este...
21715149 - The relation between the omega-3 index and arachidonic acid is bell shaped: synergistic...
21719579 - Different fatty acids inhibit apob100 secretion by different pathways: unique roles for...
8360879 - Nonpeptide angiotensin ii receptor antagonists. synthesis and biological activity of po...
15848439 - Pfgse-nmr study of the self-diffusion of sucrose fatty acid monoesters in water.
22370539 - Engineering a thermostable β-1,3-1,4-glucanase from paecilomyces thermophila to improv...
2281869 - Measurement of 12(s)-hydroxy-5z,8e,10e-heptadecatrienoic acid and its metabolite 12-oxo...
23518249 - Gangliosides containing different numbers of sialic acids affect the morphology and str...
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    
Preclinical Research and Development, Astra Draco AB.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anti-Asthmatic Agents / pharmacokinetics*
Budesonide / pharmacokinetics*
Chromatography, Liquid
Esters / chemistry,  metabolism
Fatty Acids / chemistry,  metabolism*
Lipase / chemistry
Lung / metabolism*,  ultrastructure
Mass Spectrometry
Microsomes / metabolism*
Microsomes, Liver / metabolism*
Reg. No./Substance:
0/Anti-Asthmatic Agents; 0/Esters; 0/Fatty Acids; 51333-22-3/Budesonide; EC

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

Previous Document:  Studies on the interactions of chiral secondary alcohols with rat hydroxysteroid sulfotransferase ST...
Next Document:  Synthesis and reactivity of coumarin 3,4-epoxide.