Pharmacokinetics of prednisone and prednisolone at steady state in the rabbit.

A range (approximately 0.2-2.0 micrograms/min/kg) of constant rate iv infusions of prednisolone (as the phosphate ester) was administered to five rabbits either singly or as two consecutive infusions, and then again at about the same rates of infusion as part of multiple infusion studies. Prednisone (as the succinate) was also infused at three different infusion rates (range, 1.5-15 micrograms/min/kg) to four of the five rabbits. Plasma concentrations of prednisolone and prednisone at steady state were measured by HPLC. The binding of prednisone and prednisolone in plasma was measured by equilibrium dialysis. The multiple infusion studies demonstrated that the nonlinearity in plasma clearance of prednisolone could not be attributed to any time-dependent effect. The average plasma clearance of prednisolone increased by 250% when its rate of infusion was increased 10-fold. The ranges of clearance values at low and high rates of infusion were 2.51-4.08 and 6.08-10.98 ml/min/kg, respectively. The binding of prednisolone in plasma was found to be concentration dependent. At the lower rates of infusions, the clearance of unbound prednisolone appeared to increase on increasing its rate of infusion but remained relatively constant thereafter (greater than 1.0 microgram/min/kg). The ranges of unbound plasma prednisolone clearance at low and high rates of infusions were 30.3-67.7 and 50.6-110.2 ml/min/kg, respectively. The percentage of unbound prednisone increased on increasing the total plasma prednisone concentration (ranges at low and high concentrations of prednisone were 15.5-33.7 and 32.3-47.6%).(ABSTRACT TRUNCATED AT 250 WORDS)