METABOLIC PATHWAYS OF THE TOPICAL GLUCOCORTICOID BUDESONIDE IN MAN

Google Scholar
  • 1 January 1983
    • journal article
    • research article
    • Vol. 11  (6) , 590-596
Abstract
The metabolic pathways of budesonide[(22RS)-16.alpha.,17.alpha.-butylidenedioxy-11.beta.,21-dihydroxypregna-1,4-diene-3,20-dione] in human liver 9000 g supernatant fraction were studied. A comparison was made between the in vitro metabolite pattern and the metabolite pattern in plasma obtained after i.v. administration of 3H- budesonide to man. No qualitative difference could be found, which indicates that the in vitro model is useful to predict results in vivo. The 2 major metabolites formed in vitro were identified by HPLC [high performance liquid chromatography] and mass spectrometry as 6.beta.-hydroxybudesonide and 16.alpha.-hydroxyprednisolone. Loss of the acetal group was not observed when desonide (11.beta.,21-dinydroxy-16.alpha.,17.alpha.-isopropylidenedioxypregna-1,4-diene-3,20-dione) was incubated with human liver 9000 g supernatant fraction. Neither could 16.alpha.-hydroxyprednisolone be detected after incubation of the (22S)-epimer of budesonide with the same medium. The cleavage of the acetal moiety is therefore suggested to be the result of a substrate-selective metabolic pathway.