H C Ko1, R R Almon, W J Jusko. 1. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, New York 14260, USA.
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.
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.
Authors: Katherine A Barraclough; Nicole M Isbel; Brett C McWhinney; Jacobus P J Ungerer; Gregory Medley; David W Johnson; Carmel M Hawley; Diana R Leary; Scott B Campbell; Christine E Staatz Journal: Eur J Clin Pharmacol Date: 2011-06-09 Impact factor: 2.953