A Pharmacometric Workflow for Resolving Model Instability in Model Use‐Reuse Settings
The development of fit-for-purpose pharmacokinetic-pharmacodynamic (PKPD) models based on clinical and pre-clinical data is a critically important process in model informed drug development. This process is often hampered by modeling stability issues that are often multifactorial in nature and difficult to overcome, leading to protracted model building and arbitrary simplification of the model. This tutorial provides a heuristic workflow to help identify and resolve issues relating to model instability. The approach is centered on analyses undertaken using NONMEM, but the concepts can be generalized to other software used for population analysis of pharmacokinetics (PK) or PKPD data.
Authors
- Hailemichael Zeru Hishe (ORCID: https://orcid.org/0000-0002-8557-2766)
- Ahmed Aliyu Abulfathi (ORCID: https://orcid.org/0000-0002-2089-3614)
- Stephen B. Duffull (ORCID: https://orcid.org/0000-0002-6545-9408)
- Xiao Zhu (ORCID: https://orcid.org/0000-0003-3295-619X)
- Daniel F. B. Wright (ORCID: https://orcid.org/0000-0001-9313-9252)
- Xin Liu (ORCID: https://orcid.org/0000-0002-1756-887X)
Institutions
- The University of Sydney (AU)
- Fudan University (CN)
- St Vincent's Hospital Melbourne (AU)
- St Vincent's Hospital Sydney (AU)
- Certara (United States) (US)
- St Vincent's Clinic (AU)
- Integra LifeSciences (United States) (US)
Publication Details
- Journal
- CPT Pharmacometrics & Systems Pharmacology
- Published
- 2025-06-27
- DOI
- https://doi.org/10.1002/psp4.70049
- Citations
- 3
- Primary Topic
- Pharmacogenetics and Drug Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 4.67