The effect of moderately severe hemodilution with Fluosol-DA on cytochrome P-450 mediated antipyrine metabolism.
Antipyrine metabolism was determined in conscious, unrestrained rats after isovolemic hemodilution with FluosolR-DA. Rats received an intravenous antipyrine dose (20 mg/kg) 0.5, 24, 48, or 72 hours after hemodilution and the pharmacokinetic parameters were compared to non-exchanged control (CONT) animals. Antipyrine clearance (Cl) was significantly decreased at 0.5 and 72 hours after hemodilution. Hemodilution did not significantly alter the antipyrine apparent volume of distribution (Vd) for 48 hours; however, Vd was significantly decreased by 60% at 72 hours. The cytochrome P-450 mediated formation of 3OHME and 4OH was significantly increased at 48 and 72 hours due to an increased metabolite formation rate constant (kf) and not an enhanced metabolic clearance (Clm).
Shrewsbury
R P
RP
Division of Pharmaceutics, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
Oliver
S R
SR
White
L G
LG
D000818:Animals; D000983:Antipyrine / Q000378:metabolism* / Q000493:pharmacokinetics; D001802:Blood Substitutes / Q000009:adverse effects*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004338:Drug Combinations / Q000009:adverse effects; D005466:Fluorocarbons / Q000009:adverse effects*; D006438:Hemodilution / Q000009:adverse effects*; D006895:Hydroxyethyl Starch Derivatives; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D003577:Cytochrome P-450 Enzyme System; D000983:Antipyrine