The effects of norepinephrine and prostaglandin E-1 on pharmacokinetics oflidocaine in isolated perfused rat liver

We hypothesized that depression of liver function by norepinephrine can be improved by prostaglandin E-1.Isolated perfused rat liver was selected as a n experimental model, since the flow rate can be regulated in it. Twenty-on e rats were randomly allocated to three groups: control, norepinephrine, an d norepinephrine and prostaglandin E-1 groups. The liver was perfused in a recirculating system at a constant flow rate of 20 ml/min. After administra tion of two milligrams of lidocaine in each group, lidocaine and monoethylg lycinexylidide concentrations in the recirculating system were measured, Li docaine pharmacokinetics were analyzed using the SAAM II (R) program, inclu ding metabolic rate from lidocaine to monoethylglycinexylidide using time-c oncentration curves. Norepinephrine significantly increased perfusion press ure and the area under the time-concentration curve for lidocaine. Norepine phrine decreased the clearance and the elimination rate constant of lidocai ne compared with those in the control group. Although administration of pro staglandin E-1 after infusion of norepinephrine did not significantly chang e perfusion pressure, it significantly (p < 0.05) improved metabolic rate, clearance and the elimination rate constant of lidocaine in the isolated ra t liver model. <(c)> 2001 Elsevier Science Inc. All rights reserved.