Liver metabolism of budesonide in rat, mouse, and man. Comparative aspects.
The metabolism of budesonide, (22RS)-16 alpha, 17 alpha-butylidenedioxy-11 beta,21-dihydroxypregna-1,4-diene- 3,20-dione, was studied in the 9000g supernatant fraction of livers from rat, mouse, and man. The two budesonide C-22 epimers produced different metabolites. This was explained by substrate-selective oxidation of the nonsymmetric 16 alpha, 17 alpha-acetal substituent. Epimer 22R gave 16 alpha-hydroxyprednisolone, while epimer 22S produced a metabolite tentatively identified as 23-hydroxybudesonide. Otherwise, budesonide followed the general metabolic pathways reported for synthetic glucocorticoids. Thus, oxidative metabolism predominated, 6 beta-hydroxybudesonide and delta 6-budesonide being identified in all investigated species. Reductive metabolism, giving 4,5 beta-dihydrobudesonide and 3,4,5 beta-tetrahydrobudesonide, was most pronounced in the rat. Rates and routes of budesonide metabolism were most similar in mouse and human livers. This implies that the mouse is a more relevant species than the rat in studies of the pharmacology and toxicology of budesonide.
D000368:Aged; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D001711:Biotransformation; D019819:Budesonide; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010084:Oxidation-Reduction; D011282:Pregnenediones / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012737:Sex Factors; D013045:Species Specificity
D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; D011965:Receptors, Glucocorticoid; D019819:Budesonide