Effect of corticosteroid binding globulin on the pharmacokinetics of prednisolone in rats

Abstract

Purpose: The effect of exogenous corticosteroid binding globulin (CBG) on the pharmacokinetics of intravenous prednisolone was determined in rats to test the "free hormone hypothesis."

Methods: A dose of CBG to yield 95% binding with 1000 ng/ml of prednisolone in vitro in rat plasma or saline was administered before dosing 2 mg/kg of prednisolone hemisuccinate or methylprednisolone intravenously. Drug concentrations in plasma samples were assayed by HPLC.

Results: Single administration of CBG decreased apparent prednisolone clearance by 56% (155 to 66 ml/min/kg) and reduced apparent VSS by 35% (4.1 to 2.7 L/kg) (p < 0.001). Methylprednisolone pharmacokinetics, studied as a negative control because the drug does not bind to CBG, did not change.

Conclusions: The corticosteroid bound to CBG does not appear to be available for removal by clearance organs.