In the Cradle of Pharmacometric Methodology: Introducing Population PKPD Modeling, Simultaneous Analysis, and the Effect-Compartment Model-Commentary on Sheiner et al.

In the decades preceding 1970s, there were considerable advances in theoretical descriptions of pharmacokinetics, drug action, and the time-course of dose-concentration-response relations. However, delayed drug effects and how to analyze data across individuals still offered a considerable challenge. Sheiner et al., through the formulation of the effect-compartment model, the utilization of nonlinear mixed effects models, and simultaneous PKPD analysis, offered solutions to these issues that still today are considered state-of-the-art.