ArticleCPT: pharmacometrics & systems pharmacology2014
Incorporating Target Shedding Into a Minimal PBPK-TMDD Model for Monoclonal Antibodies.
Article in CPT: pharmacometrics & systems pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Using Virtual Patients to Evaluate Dosing Strategies for Bispecifics With a Bell-Shaped Efficacy Curve.CPT: pharmacometrics & systems pharmacology · 2025Article
- The quest for balance between capturing data and model complexity: A quantitative clinical pharmacology approach applied to monoclonal antibodies.CPT: pharmacometrics & systems pharmacology · 2023Article
- Mathematical Models to Characterize the Absorption, Distribution, Metabolism, and Excretion of Protein Therapeutics.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- A Physiologically Based Pharmacokinetic Framework for Quantifying Antibody Distribution Gradients from Tumors to Tumor-Draining Lymph Nodes.Antibodies (Basel, Switzerland) · 2022Article
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- Mechanistic Quantitative Pharmacology Strategies for the Early Clinical Development of Bispecific Antibodies in Oncology.Clinical pharmacology and therapeutics · 2020Review
- Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development.Drug metabolism and pharmacokinetics · 2019Review
- Dual Function pH Responsive Bispecific Antibodies for Tumor Targeting and Antigen Depletion in Plasma.Frontiers in immunology · 2019Article
- The Spectrum of Mechanism-Oriented Models and Methods for Explanations of Biological Phenomena.Processes (Basel, Switzerland) · 2018Article
- Article
- Population PBPK modelling of trastuzumab: a framework for quantifying and predicting inter-individual variability.Journal of pharmacokinetics and pharmacodynamics · 2017Article
- Assessing the Impact of Tissue Target Concentration Data on Uncertainty in In Vivo Target Coverage Predictions.CPT: pharmacometrics & systems pharmacology · 2016Article
- Potential Sources of Inter-Subject Variability in Monoclonal Antibody Pharmacokinetics.Clinical pharmacokinetics · 2016Review
- A PBPK model describing a xenobiotic with a short PK event scale.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Simulation of monoclonal antibody pharmacokinetics in humans using a minimal physiologically based model.The AAPS journal · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shedding of a pharmacological target from cells, giving rise to a soluble target that can also bind therapeutic proteins, is a common phenomenon. In this study, a minimal physiologically based pharmacokinetic model was used to simulate the pharmacokinetics of trastuzumab and the simultaneous binding of the compound to soluble (in blood and tissue interstitial space) and membrane-bound (in the tissue interstitial space) forms of human epidermal growth factor receptor 2 (HER2). The parameter values describing binding of trastuzumab to HER2 were largely derived from in vitro data, and the effects of varying HER2 levels, the affinity difference between membrane-bound HER2 and shed antigen, and slow binding kinetics were investigated. The model simulates a sharp decrease in trough drug concentrations at concentrations of soluble target between 500 and 1,000 ng/ml in plasma. This corresponds with the clinical concentration range of soluble target wherein changes in half-life of trastuzumab have been observed.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e96; doi:10.1038/psp.2013.73; published online 29 January 2014.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.