Abstract

The purposes of this study were: 1) to determine in dogs under steady-state conditions whether prednisolone clearance increases with increasing dose as has been suggested from results obtained under nonsteady-state conditions in man and 2) to determine whether the prednisolone to prednisone conversion, apparently resulting from 11 beta-hydroxydehydrogenase, is saturable. Six dogs were given four different zero-order infusions of prednisolone resulting in steady-state levels from 23 to 5884 ng/ml.Prednisone, total and free prednisolone levels were assessed by high-pressure liquid chromatography and equilibrium dialysis. Total and unbound prednisolone clearances were calculated by dividing the infusion rate by the total or unbound prednisolone concentration at steady state. Both total and unbound prednisolone clearance exhibited a slight tendency to decrease (P < .05) with increasing prednisolone steady-state levels. The conversion of prednisolone to prednisone, defined by the prednisolone/prednisone ratio, exhibited saturable characteristics which, when data for all dogs was fitted to a Michaelis-Menten type equation (r2 = 0.938), gave a Km of 658 ng/ml, i.e., total prednisolone concentration at half-maximal saturation.