PREDNISOLONE CLEARANCE AT STEADY-STATE IN DOGS

  • 1 January 1980
    • journal article
    • research article
    • Vol. 215  (2) , 287-291
Abstract
The purposes of this study were to determine under steady-state conditions in dogs whether prednisolone plasma clearance increases with increasing dose, as suggested from results obtained under nonsteady-state conditions in man, and to determine whether the prednisolone to prednisone conversion, apparently due to 11 .beta.-hydroxydehydrogenase, is saturable. Six dogs were given 4 different zero-order infusions of prednisolone, causing steady-state levels from 23-5884 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 < 0.05) 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.

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