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Tutorial for Modeling Delays in Biological Systems in the NONMEM Software

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Title: Tutorial for Modeling Delays in Biological Systems in the NONMEM Software
Authors: Robert J. Bauer, Wojciech Krzyzanski
Source: CPT Pharmacometrics Syst Pharmacol
CPT: Pharmacometrics & Systems Pharmacology, Vol 14, Iss 7, Pp 1133-1155 (2025)
Publisher Information: Wiley, 2025.
Publication Year: 2025
Subject Terms: distributed delay systems, delay differential equations, Tutorial, biostatistics, Therapeutics. Pharmacology, RM1-950, nonlinear models, NONMEM, pharmacometrics
Description: Delays in biological systems are a common phenomenon. The models for delays require specialized mathematical and numerical techniques such as transit compartments, delay differential equations (DDEs), and distributed DDEs (DDDEs). Because of mathematical complexity, DDEs and particularly DDDEs are infrequently used for modeling. DDEs are supported by most pharmacometric programs. Recently, DDDEs have been implemented in NONMEM that greatly improve the applicability of this technique in pharmacokinetic and pharmacodynamic (PKPD) modeling. The objective of this tutorial is to provide examples of PKPD models with delays and demonstrate how to implement them in NONMEM. All examples provide a brief description of the biology and pharmacology underlying model equations, explain how they are coded in the NONMEM control stream, and discuss results of data analysis models were used for. NONMEM codes for all models are presented in supporting information (Data S1). The tutorial concludes with a discussion of the pros and cons of presented delay modeling techniques with guidelines for which one might be preferred given the nature of the delay, available data, and the task to be performed.
Document Type: Article
Other literature type
Language: English
ISSN: 2163-8306
DOI: 10.1002/psp4.70046
Access URL: https://doaj.org/article/b5db51206fef49939bc930b9cd692608
Rights: CC BY NC ND
URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Accession Number: edsair.doi.dedup.....8dccd3ddaab482b0c7d8b87f81dba9a7
Database: OpenAIRE
Description
Abstract:Delays in biological systems are a common phenomenon. The models for delays require specialized mathematical and numerical techniques such as transit compartments, delay differential equations (DDEs), and distributed DDEs (DDDEs). Because of mathematical complexity, DDEs and particularly DDDEs are infrequently used for modeling. DDEs are supported by most pharmacometric programs. Recently, DDDEs have been implemented in NONMEM that greatly improve the applicability of this technique in pharmacokinetic and pharmacodynamic (PKPD) modeling. The objective of this tutorial is to provide examples of PKPD models with delays and demonstrate how to implement them in NONMEM. All examples provide a brief description of the biology and pharmacology underlying model equations, explain how they are coded in the NONMEM control stream, and discuss results of data analysis models were used for. NONMEM codes for all models are presented in supporting information (Data S1). The tutorial concludes with a discussion of the pros and cons of presented delay modeling techniques with guidelines for which one might be preferred given the nature of the delay, available data, and the task to be performed.
ISSN:21638306
DOI:10.1002/psp4.70046