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Journal of Pharmacokinetics and Pharmacodynamics

, Volume 44, Issue 5, pp 415–423 | Cite as

Deterministic identifiability of population pharmacokinetic and pharmacokinetic–pharmacodynamic models

  • Vijay K. SiripuramEmail author
  • Daniel F. B. Wright
  • Murray L. Barclay
  • Stephen B. Duffull
Original Paper

Abstract

Identifiability is an important component of pharmacokinetic–pharmacodynamic (PKPD) model development. Structural identifiability is concerned with the uniqueness of the model parameters for a set of perfect input–output data and deterministic identifiability with the precision of parameter estimation given imperfect input–output data. We introduce two subcategories of deterministic identifiability, external and internal, and consider factors that distinguish between these forms. We define external deterministic identifiability as a function of externally controllable variables, i.e., the design, and internal deterministic identifiability as a function of the model and its parameter values. The concepts are explored using three common PK and PKPD models, and verified for their precision for the selected set of parameter values under optimal design.

Keywords

Identifiability Parameter precision Population analysis PKPD models Optimal study design NONMEM 

Notes

Acknowledgements

Vijay K Siripuram is supported by University of Otago postgraduate scholarship.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10928_2017_9530_MOESM1_ESM.docx (293 kb)
Supplementary material 1 (DOCX 293 kb)

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Otago Pharmacometrics Group, School of PharmacyUniversity of OtagoDunedinNew Zealand
  2. 2.Departments of Gastroenterology & Clinical PharmacologyChristchurch HospitalChristchurchNew Zealand

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