Lidocaine disposition kinetics in monkey and man; II. Effects of hemorrhage and sympathomimetic drug administration

Lidocaine disposition kinetics in normal and hemorrhaged rhesus monkeys was studied. During bleeding there was a reduction in distribution and clearance of lidocaine, along with an increase in half‐life, which was similar to that in human patients with congestive heart failure. In the monkey in shock there was impaired liver extraction of lidocaine. Sympathomimetic drugs, such as isoproterenol and norepinephrine, which influence hepatic blood flow, markedly altered clearance and steady‐state lidocaine concentrations in blood. A perfusion model that simulates blood and tissue levels during hemorrhage in monkey and man by using blood flow measurements during hemorrhagic shock is reported here. This perfusion model allowed a quantitative understanding of the interaction between lidocaine and sympathomimetic drugs and may be clinically useful in man simultaneously receiving a variety of cardioactive drugs ill suggesting appropriate ad;ustments of the dosages of the most critical drugs used.