Edsbäcker S, Jönsson S, Lindberg C, Ryrfeldt A, Thalén A
Drug Metab Dispos. 1983 Nov-Dec;11(6):590-6.
The metabolic pathways of budesonide[(22RS)-16 alpha, 17 alpha-butylidenedioxy-11 beta, 21-dihydroxypregna-1,4-diene-3,20-dione] in human liver 9000g supernatant fraction were studied. A comparison was made between the in vitro metabolite pattern and the metabolite pattern in plasma obtained after iv administration of tritiated budesonide to man. No qualitative difference could be found, which indicates that the in vitro model is useful to predict results in vivo. The two major metabolites formed in vitro were identified by HPLC and mass spectrometry as 6 beta-hydroxybudesonide and 16 alpha-hydroxyprednisolone. Loss of the acetal group was not observed when desonide (11 beta,21-dihydroxy-16 alpha,17 alpha-isopropylidenedioxy-pregna-1,4-diene-3,20-dione) was incubated with human liver 9000g 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.
研究了布地奈德[（22RS）-16α，17α-亚丁基二氧基-11β，21-二羟基孕甾-1,4-二烯-3,20-二酮]在人肝脏9000g上清液组分中的代谢途径。将体外代谢产物模式与氚标记的布地奈德静脉注射给人后血浆中的代谢产物模式进行了比较。未发现定性差异，这表明体外模型可用于预测体内结果。通过高效液相色谱法和质谱法将体外形成的两种主要代谢产物鉴定为6β-羟基布地奈德和16α-羟基泼尼松龙。当地索奈德（11β，21-二羟基-16α，17α-异丙叉二氧基-孕甾-1,4-二烯-3,20-二酮）与人肝脏9000g上清液组分一起孵育时，未观察到缩醛基团的丢失。布地奈德的（22S）-差向异构体与相同培养基孵育后也未检测到16α-羟基泼尼松龙。因此，缩醛部分的裂解被认为是底物选择性代谢途径的结果。
