Lidocaine disposition kinetics in monkey and man; I. Prediction by a perfusion model

Abstract

Lidocaine pharmacokinetics are described in the unanesthetized restrained rhesus monkey after bolus and steady infusion. Simultaneous measurements of systemic and regional blood flows and tissue masses were made in the same animals. Physiologic data are combined in a perfusion model that is predictive of kinetics of lidocaine in the mankey. The model uses eight tissue compartments. Concentrations of lidocaine are described in various tissues at various times. In the first seconds after an intravenous bolus, much at the lidocaine is sequestered by the lungs; then by heart and kidneys and other rapidly perfused tissues. Redistribution then occurs into skeletal muscle and adipose tissue, which accounts for the long observed half‐life of lidocaine. Blood flow and tissue composition data from monkeys can be applied to man to predict blood levels of lidocaine after intravenous injection. The perfusion model is therefore potentially useful in describing and predicting blood levels in states of cardiovascular disease in both monkey and man.