REVERSIBLE FORMATION OF FATTY-ACID ESTERS OF BUDESONIDE, AN ANTIASTHMA GLUCOCORTICOID, IN HUMAN LUNG AND LIVER-MICROSOMES

Microsomes from human lung and liver catalyze the formation of fatty a cid esters of budesonide, a glucocorticoid used for inhalation treatme nt of asthma, The conjugation was dependent on coenzyme A and ATP, Add ition of free fatty acids to the incubations affected the pattern of m etabolites, but ester formation was observed also without such additio n, Budesonide oleate, palmitate, linoleate, palmitoleate, and arachido nate were identified as metabolites, The fatty acid conjugates of bude sonide were shown to be substrates for lipase in vitro, thus budesonid e is regainable from the conjugates. The data suggest that an equilibr ium between budesonide and these pharmacologically inactive lipoidal c onjugates will be established in tissues at repeated exposure to budes onide. Since the fatty acid conjugates most likely will be retained in tracellularly for a longer time than unchanged budesonide, the duratio n of tissue exposure to budesonide will depend partly on the rate of l ipase-catalyzed hydrolysis of the conjugates. The findings in this stu dy provide a possible explanation for the efficacy of budesonide in mi ld asthmatics also when inhaled once daily.