Article date: June 2017
By: Mario González‐Sales, Fahima Nekka, Mario Tanguay, Pierre‐Olivier Tremblay, Jun Li in Volume 83, Issue 6, pages 1240-1251
Aims
The aim of this paper is to investigate the role of drug concentration samplings in the modelling of the dose–response relationship.
Methods
Using 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.
Results
K‐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.
Conclusions
K‐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.
DOI: 10.1111/bcp.13225
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