An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models

摘要

AbstractMathematical models are routinely used in clinical pharmacology to study the pharmacokinetic and pharmacodynamic properties of a drug in the body. Identifiability of these models is an important requirement for the success of these clinical studies. Identifiability is classified into two types, structural identifiability related to the structure of the mathematical model and deterministic identifiability which is related to the study design. There are existing approaches for assessment of structural identifiability of fixed-effects models, although their use appears uncommon in the literature. In this study, we develop an informal unified approach for simultaneous assessment of structural and deterministic identifiability for fixed and mixed-effects pharmacokinetic or pharmacokinetic–pharmacodynamic models. This approach uses an information theoretic framework. The method is applied both to simple examples to explore known identifiability properties and to a more complex example to illustrate its utility.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e49; doi:10.1038/psp.2013.25; advance online publication 19 June 2013