The Effect of Moderately Severe Hemodilution with Fluosol-DA on Cytochrome P-450 Mediated Antipyrine Metabolism

Abstract

Antipyrine metabolism was determined in conscious, unrestrained rats after isovolemic hemodilution with Fluosol^R-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 (V_d) for 48 hours; however, V_d 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 (k_f) and not an enhanced metabolic clearance (Cl_m).