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.
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Ko, H.C., Almon, R.R. & Jusko, W.J. Effect of Corticosteroid Binding Globulin on the Pharmacokinetics of Prednisolone in Rats. Pharm Res 12, 902–904 (1995). https://doi.org/10.1023/A:1016225423795
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DOI: https://doi.org/10.1023/A:1016225423795