Modelling the dose–response relationship: the fair share of pharmacokinetic and pharmacodynamic information

Abstract

AimsThe aim of this paper is to investigate the role of drug concentration samplings in the modelling of the dose–response relationship.MethodsUsing an initial PK/PD model, a reference dataset was simulated. PK and PD samples were extracted to create reduced datasets. PK/PD and K‐PD models were fitted to theses reduced datasets. Post hoc estimates from both types of models were compared to the initial PK/PD model and performance was assessed.ResultsK‐PD models were largely biased when the drug has a nonlinear elimination. PK/PD models with 1 PK and 2 PD samples were superior to K‐PD models with 3 PD samples. PK/PD models with 1 or 2 PK samples and 3 PD samples proved to be superior to K‐PD models with 4 PD samples.ConclusionsK‐PD models should not be used when the drug has nonlinear elimination. K‐PD models should not replace PK/PD modelling but are an alternative approach if the PD information is large enough.