Automated Scale Reduction of Nonlinear QSP Models With an Illustrative Application to a Bone Biology System
Open accessAbstract
Integrating quantitative systems pharmacology (QSP) into pharmacokinetics/pharmacodynamics (PKPD) has resulted in models that are highly complex and often not amenable to further exploration via estimation or design. Because QSP models are usually depicted using nonlinear differential equations it is not straightforward to apply some model reduction techniques, such as proper lumping. In this study, we explore the combined use of linearization and proper lumping as a general method to simplification of a nonlinear QSP model. We illustrate this with a bone biology model and the reduced model was then applied to describe bone mineral density (BMD) changes due to denosumab dosing. The methodologies used in this study can be applied to other multiscale models for developing a mechanism‐based structural model for future analyses.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 31 · Cited by 18
- Authors
- Hasegawa, C., & Duffull, S. B.
- Affiliations
- Ono Pharmaceutical (Japan) (JP)
- University of Otago (NZ)
- Corresponding author
- Hasegawa, Chihiro
- Venue
- CPT: Pharmacometrics & Systems Pharmacology
- Publisher
- Wiley
- Published
- 2018-08-13
- Volume
- 7
- Issue
- 9
- Pages
- 562-572
- ISSN
- 2163-8306 (ISSN-L)
- PMC
- PMC6157701
- OpenAlex
- W2884298927
- Cited by
- 18
- References
- 31
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 3 · 2017: 1
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- CPT Pharmacometrics & Systems Pharmacology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Modeling and Simulation Systems
- Keywords
- model reduction, quantitative systems pharmacology, nonlinear differential equations, linearization, bone mineral density, denosumab, multiscale modeling, pharmacokinetic-pharmacodynamic modeling
- MeSH terms
- Automation, Bone and Bones, Humans, Models, Biological, Pharmacokinetics, Pharmacology, Nonlinear Dynamics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
