Optimal pharmacokinetic delivery of infused drugs: application to the treatment of cardiac arrhythmias.

A common clinical goal of infusing drugs is to attain therapeutic steady-state concentrations as rapidly as possible. The desire is to closely approximate a step function in plasma concentration of the therapeutic agent. We have developed a novel approach to achieve this goal by using the principles of systems and compartmental analyses. The approach is to build a pharmacokinetic model for the disposition of the drug and then calculate backwards from the desired output function to derive the optimal input infusion function. We applied this technique to the infusion of Lidocaine, an antiarrhythmic agent which is often difficult to control. An optimal infusion function, used to drive a servo-controlled infusion pump, was derived to closely approximate a step-function response of drug levels. The efficacy of this infusion function was verified experimentally in dogs.