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 30HME and 40H was significantly increased at 48 and 72 hours due to an increased metabolite formation rate constant (kf) and not an enhanced metabolic clearance (Clm).