Pharmacokinetic and pharmacodynamic interactions between dehydroepiandrosterone and prednisolone in the rat.
The effects of multiple-dosing with dehydroepiandrosterone sulfate (DHEA-SO4) on the pharmacokinetics and pharmacodynamics of prednisolone were examined. Prednisolone (25 mg/kg i.v.) was administered to male and female Sprague-Dawley rats (250-350 g) alone and following DHEA-SO4 (4 mg/kg i.v., every 8 h for 4 days). Male control rats cleared prednisolone faster [3.68 +/- 1.30 (males) vs 1.01 +/- 0.7 l/h/kg; p < 0.05] and had larger Vss (1.38 +/- 0.459 vs 0.394 +/- 0.500 l/kg; p < 0.05) than females both due largely to lesser plasma protein binding. Prednisolone clearance and Vss were not altered by DHEA-SO4 in males or females. The net effect of prednisolone on basophils and plasma corticosterone did not differ with gender. DHEA-SO4 had no effect on plasma corticosterone and did not alter prednisolone action. DHEA-SO4 inhibited basophil trafficking in males, but to a lesser extent than prednisolone, and antagonized the effect of prednisolone on basophil trafficking in both sexes. The steroid-sparing effect observed with DHEA clinically may not be due to an alteration of corticosteroid pharmacokinetics but partly to its ability to affect immune functions.
Meno-Tetang
G M
GM
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260, USA.
Hon
Y Y
YY
Van Wart
S
S
Jusko
W J
WJ
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001491:Basophils / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D003687:Dehydroepiandrosterone; D011239:Prednisolone; D003345:Corticosterone