Abstract
Budesonide, a corticosteroid used in the treatment of asthma and allergic reactions, is almost entirely cleared by metabolism in man. We describe the sulphation of budesonide in human liver and lung and provide evidences that the sulphation of budesonide is catalysed by testosterone sulphotransferase. A rapid and reproducible radiometric assay for budesonide sulphotransferase is described. Liver specimens were obtained from 35 men and 65 women and lung specimens from 2 women and 17 men.
The average hepatic budesonide sulphation rate was significantly higher in men (41.1 pmol·min−1·ml−1) than women (28.2 pmol·min−1·mg−1). In the lung, the mean budesonide sulphation rate was 5.0 pmol·min−1·mg−1.
Testosterone strongly inhibited the hepatic sulphation of budesonide, whereas p-nitrophenol and dopamine were poor inhibitors; the IC50 was 7.0 uM (testosterone), 320 uM (p-nitrophenol) and 510 uM (dopamine). The hepatic rates of testosterone, p-nitrophenol and dopamine sulphation were measured in the same samples assayed for budesonide sulphotransferase. There was a correlation between the hepatic rates of budesonide and testosterone sulphation (P<0.001; r=0.810). The activity of testosterone sulphotransferase was significantly greater in men than women (22.0 vs. 17.2 pmol·min−1·mg−1), wheres those of dopamine and p-nitrophenol sulphotransferase were not sex dependent.
The hepatic activity of budesonide sulphotransferase parallels that of testosterone suggesting that sulphation is an important reaction in the metabolism of budesonide.
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Pacifici, G.M., Ferroni, M.A., Temellini, A. et al. Human liver budesonide sulphotransferase is inhibited by testosterone and correlates with by testosterone sulphotransferase. Eur J Clin Pharmacol 46, 49–54 (1994). https://doi.org/10.1007/BF00195915
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DOI: https://doi.org/10.1007/BF00195915