ArticleThe AAPS journal2018
A Minimal Physiologically Based Pharmacokinetic Model with a Nested Endosome Compartment for Novel Engineered Antibodies.
Article in The AAPS journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Clinical Validation of a QSP Model for ISB 2001, a Trispecific T Cell Engager to Support Optimal FIH Study Design in RRMM Patients.Clinical pharmacology and therapeutics · 2026Trial
- Prediction of Monoclonal Antibody Pharmacokinetics in Pediatric Populations Using PBPK Modeling and Simulation.Pharmaceutics · 2025Article
- Development of an mPBPK machine learning framework for early target pharmacology assessment of biotherapeutics.Scientific reports · 2025Article
- ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells.Nature cancer · 2024Article
- A minimal physiologically based pharmacokinetic model to study the combined effect of antibody size, charge, and binding affinity to FcRn/antigen on antibody pharmacokinetics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Kinetic modeling of the plasma pharmacokinetic profiles of ADAMTS13 fragment and its Fc-fusion counterpart in mice.Frontiers in pharmacology · 2024Article
- Review of the Existing Translational Pharmacokinetics Modeling Approaches Specific to Monoclonal Antibodies (mAbs) to Support the First-In-Human (FIH) Dose Selection.International journal of molecular sciences · 2022Review
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- In Translation: FcRn across the Therapeutic Spectrum.International journal of molecular sciences · 2021Review
- Development of a Pharmacokinetic Model Describing Neonatal Fc Receptor-Mediated Recycling of HL2351, a Novel Hybrid Fc-Fused Interleukin-1 Receptor Antagonist, to Optimize Dosage Regimen.CPT: pharmacometrics & systems pharmacology · 2020Article
- A systems pharmacokinetic/pharmacodynamic model for concizumab to explore the potential of anti-TFPI recycling antibodies.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Article
- Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab.Clinical pharmacokinetics · 2019Review
- Physiologically-based modeling of monoclonal antibody pharmacokinetics in drug discovery and development.Drug metabolism and pharmacokinetics · 2019Review
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
We proposed here a minimal physiologically based pharmacokinetic (mPBPK) model for a group of novel engineered antibodies in mice and humans. These antibodies are designed with altered binding properties of their Fc domain with neonatal Fc receptor (FcRn) or the Fab domain with their cognate targets (recycling antibodies) in acidic endosomes. To enable simulations of such binding features in the change of antibody pharmacokinetics and its target suppression, we nested an endothelial endosome compartment in parallel with plasma compartment based on our previously established mPBPK model. The fluid-phase pinocytosis rate from plasma to endothelial endosomes was reflected by the clearance of antibodies in FcRn dysfunctional humans or FcRn-knockout mice. The endosomal recycling rate of FcRn-bound antibodies was calculated based on the reported endosomal transit time. The nonspecific catabolism in endosomes was fitted using pharmacokinetic data of a human wild-type IgG
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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.