Effect of Fluosol-DA hemodilution on the kinetics of hepatically eliminated drugs

The pharmacokinetics of four hepatically eliminated drugs were determined in the rat following moderate hemodilution with either Fluosol-DA or normal saline. The drugs, antipyrine, phenytoin, indocyanine green, and d-propranolol, have extraction ratios from 0.01 to 0.99 in the rat. Animals received an intravenous dose of the drug 0.5, 24, 48, or 72 hours after hemodilution and drug disposition was compared to non-exchanged animals. Antipyrine clearance was increased 48 and 72 hours after Fluosol-DA exchange probably due to enhanced microsomal enzymatic activity. Indocyanine green clearance was decreased 24 hours after Fluosol-DA exchange more likely by a change in its extraction ratio than by alterations in hepatic blood flow. Phenytoin and d-propranolol clearances were decreased at 24 and 72 hours respectively after Fluosol-DA hemodilution due to a decreased apparent volume of distribution. Saline hemodilution decreased phenytoin clearance 24, 48, and 72 hours after exchange also by decreasing the apparent volume of distribution. This volume change was thought to be due to hypovolemia or a microcirculation redistribution which was secondary to hemodilution.