Simultaneous pharmacokinetic and pharmacodynamic modeling

Abstract

The compartmental model approach previously proposed by Sheiner et al. for the simultaneous characterization of the pharmacokinetics and pharmacodynamics of a drug substance has been rigorously tested and extended in the present report. Pharmacokinetic and pharmacodynamic equations were derived for several commonly used models, as well as alternate models that relate effect to drug concentrations in a peripheral compartment. The versatility and flexibility of these models were tested using simulation and curve-fitting procedures. The utility as well as the limitations of this modeling procedure are discussed.