Delay differential equations based models in NONMEM

Yan, Xiaoyu; Bauer, Robert; Koch, Gilbert; Schropp, Johannes; Pérez-Ruixo, Juan Jose; Krzyzanski, Wojciech

Delay differential equations based models in NONMEM

Dateien

Yan_2-14m1fvwpltwrp7.pdfGröße: 5.24 MBDownloads: 233

Datum

2021

Autor:innen

Yan, Xiaoyu

Bauer, Robert

Koch, Gilbert

Schropp, Johannes

Pérez-Ruixo, Juan Jose

Krzyzanski, Wojciech

Open Access-Veröffentlichung

Open Access Green

Sammlungen

Mathematik und Statistik

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Journal of Pharmacokinetics and Pharmacodynamics. Springer. 2021, 48(6), pp. 763-802. ISSN 1567-567X. eISSN 1573-8744. Available under: doi: 10.1007/s10928-021-09770-z

Zusammenfassung

Delay differential equations (DDEs) are commonly used in pharmacometric models to describe delays present in pharmacokinetic and pharmacodynamic data analysis. Several DDE solvers have been implemented in NONMEM 7.5 for the first time. Two of them are based on algorithms already applied elsewhere, while others are extensions of existing ordinary differential equations (ODEs) solvers. The purpose of this tutorial is to introduce basic concepts underlying DDE based models and to show how they can be developed using NONMEM. The examples include previously published DDE models such as logistic growth, tumor growth inhibition, indirect response with precursor pool, rheumatoid arthritis, and erythropoiesis-stimulating agents. We evaluated the accuracy of NONMEM DDE solvers, their ability to handle stiff problems, and their performance in parameter estimation using both first-order conditional estimation (FOCE) and the expectation–maximization (EM) method. NONMEM control streams and excerpts from datasets are provided for all discussed examples. All DDE solvers provide accurate and precise solutions with the number of significant digits controlled by the error tolerance parameters. For estimation of population parameters, the EM method is more stable than FOCE regardless of the DDE solver.

Fachgebiet (DDC)

510 Mathematik

Zitieren

ISO 690

YAN, Xiaoyu, Robert BAUER, Gilbert KOCH, Johannes SCHROPP, Juan Jose PÉREZ-RUIXO, Wojciech KRZYZANSKI, 2021. Delay differential equations based models in NONMEM. In: Journal of Pharmacokinetics and Pharmacodynamics. Springer. 2021, 48(6), pp. 763-802. ISSN 1567-567X. eISSN 1573-8744. Available under: doi: 10.1007/s10928-021-09770-z

BibTex

@article{Yan2021-12Delay-54527,
  year={2021},
  doi={10.1007/s10928-021-09770-z},
  title={Delay differential equations based models in NONMEM},
  number={6},
  volume={48},
  issn={1567-567X},
  journal={Journal of Pharmacokinetics and Pharmacodynamics},
  pages={763--802},
  author={Yan, Xiaoyu and Bauer, Robert and Koch, Gilbert and Schropp, Johannes and Pérez-Ruixo, Juan Jose and Krzyzanski, Wojciech}
}

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