Kinetics of the epimeric glucocorticoid budesonide

Abstract
Budesonide is a potent nonhalogenated glucocorticoid consisting of a l/l mixture of the 2 epimers, 22R and 22S. The kinetics of these epimers were studied in 6 healthy male subjects after i.v. administration of 500 .mu.g 3H-budesonide. Estimation of the epimer concentrations in plasma was made possible by development of an HPLC [high performance liquid chromatography] method for simultaneous separation and quantification. The plasma t1/2 [half life], distribution volume (V.beta.), and plasma clearance for epimer 22R were (mean) 2.66 .+-. 0.57 h, 425 .+-. 100 l and 117 .+-. 40 l/h. The corresponding values for epimer 22S were 2.71 .+-. 0.69 h, 245 .+-. 38 l and 67 .+-. 19 l/h. Differences in V.beta. and plasma clearance between the 2 were significant. The larger V.beta. noted for epimer 22R may be a result of higher tissue affinity. The high plasma clearance for both epimers should largely reflect their high rate of liver biotransformation.