Inequality of Clearance Values Obtained by Intravenous Bolus and by Steady-State Infusion

In order to compare total and free prednisolone clearance values following an intravenous bolus dose with those following zero-order infusions to steady state, 6 dogs were given an intravenous bolus and four different zero-order infusions of prednisolone. Prednisolone clearance for the infusion studies were calculated by dividing the infusion rate by the steady-state concentration. Time-averaged clearances for the intravenous bolus doses were calculated as dose divided by area under the concentration curve. The total and unbound prednisolone clearance values calculated using the steady-state levels averaged 24 and 39% higher, respectively, than the corresponding clearance values obtained following intravenous bolus dosing.