Effect of corticosteroid binding globulin on the pharmacokinetics of prednisolone in rats.
OBJECTIVE
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.
Ko
H C
HC
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, New York 14260, USA.
Almon
R R
RR
Jusko
W J
WJ
D000818:Animals; D007275:Injections, Intravenous; D008297:Male; D008775:Methylprednisolone / Q000493:pharmacokinetics; D011239:Prednisolone / Q000493:pharmacokinetics*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014156:Transcortin / Q000494:pharmacology*
D014156:Transcortin; D011239:Prednisolone; D008775:Methylprednisolone