In vitro biotransformation of glucocorticoids in liver and skin homogenate fraction from man, rat and hairless mouse.

The pharmacological effects of glucocorticoids are greatly influenced by their pharmacokinetic properties. In the present report, the in vitro biotransformation of the topical glucocorticoids [3H]-budesonide ([3H]-BUD). [3H]-triamcinolone acetonide ([3H]-TAAc) and [3H]-hydrocortisone ([3H]-HC) was studied in the 9000 g liver and skin supernatant from man, rat and hairless mouse. The rate of disappearance of the compounds was estimated during the initial 30 min of incubation by high performance liquid chromatography. In human liver the half life (t1/2) rank order was [3H]-BUD (7--23 min) less than [3H]-TAAc (13--68 min) less than [3H]-HC (40--67 min), in rat liver [3H]-HC (14--21 min) less than [3H]-BUD (28--38 min) less than [3H]-TAAc (161--196 min) and in hairless mouse liver [3H]-BUD (17--22 min) less than [3H]-TAAc (21--34 min) less than [3H]-HC (82--165 min). Negligible biotransformation of these glucocorticoids occurred in skin. BUD is a one to one mixture of the [22R]- and [22S]-epimers. It was found that the [22R]-epimer was more susceptible to liver biotransformation than the [22S]-epimer of [3H]-BUD. The results are discussed with particular reference to the extent of systemic side effects of these compounds.