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Modelling the dose–response relationship: the fair share of pharmacokinetic and pharmacodynamic information
Author(s) -
GonzálezSales Mario,
Nekka Fahima,
Tanguay Mario,
Tremblay PierreOlivier,
Li Jun
Publication year - 2017
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13225
Subject(s) - pharmacokinetics , pharmacodynamics , pharmacology , drug , chemistry , medicine
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.