Pharmacokinetic and pharmacodynamic modeling in anesthesia

Abstract

Before 1950, we little understood what drugs did to patients (pharmacodynamics) or what patients did to drugs (pharmacokinetics). In 1949, Faulconer et al correlated the EEG with the sedative/anesthetic effects of nitrous oxide. In 1960, Price simulated thiopental pharmacokinetics. In 1963, Eger extended the simulation to inhaled anesthetics and invented MAC. From 1972 to 1997, Sheiner and Rosenberg used computer models to predict pharmacokinetics in individuals, leading to the population principle. In 1978, Hull used the effect site concept to understand the time course of pancuronium's effect. From 1978 to 1986, Sheiner and Beal defined methods for estimating the parameters controlling drug behavior, developing NONMEM to estimate population pharmacokinetics. In the 1980s, Schwilden published models allowing control of anesthetic concentrations. With Stoeckel, he devised a target controlled infusion (TCI) system that could maintain a target drug concentration.