Biotransformation in vitro of the 22R and 22S epimers of budesonide by human liver, bronchus, colonic mucosa and skin

The pharmacological effects of glucocorticoids are greatly influenced by th eir pharmacokinetic properties. In the present report, the in vitro biotran sformation of the 22R and 22S epimers of the topical steroid budesonide was studied in the S-9 fraction of human liver, bronchus, skin and colonic muc osa. The disappearance of unchanged epimers of budesonide was measured during 90 min of incubation by high performance liquid chromatography. The rate of d isappearance was high in human liver while little biotransformation occurre d in bronchial tissue and colonic mucosa, and none was detected in the skin , A marked decay of the initial concentration of unchanged budesonide epime rs was noticed after 2 h incubation in cultured human hepatocytes, while on ly a small decrease was observed after 24 h incubation in cultured human ai rway smooth muscle cells and BEAS-2B cells. The 22R epimer of budesonide su ffered greater in vitro biotransformation than the 22S epimer in human hepa tic, bronchial and colonic tissues. These findings extend those of other studies, and confirm that the high the rapeutic ratio of budesonide is due to negligible local biotransformation c ombined with high level of liver metabolism for locally absorbed budesonide .