ArticleJournal of pharmacokinetics and pharmacodynamics2022
Towards a translational physiologically-based pharmacokinetic (PBPK) model for receptor-mediated transcytosis of anti-transferrin receptor monoclonal antibodies in the central nervous system.
Article in Journal of pharmacokinetics and pharmacodynamics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Blood-Brain Barrier Regulation: Evolving From Classic Strategies to Electrochemical Ion and Reactive Oxygen Species Control.Advanced healthcare materials · 2026Review
- Article
- On the coupling between a basic FcRn mechanism and target-mediated disposition of antibodies.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Effect of FcRn Binding on Monoclonal Antibody Disposition in the Brain.The AAPS journal · 2025Article
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Computational neurosciences and quantitative systems pharmacology: a powerful combination for supporting drug development in neurodegenerative diseases.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Investigation of Antibody Pharmacokinetics in the Brain Following Intra-CNS Administration and Development of PBPK Model to Characterize the Data.The AAPS journal · 2024Article
- Physiologically Based Pharmacokinetic Modeling to Characterize the Effect of Molecular Charge on Whole-Body Disposition of Monoclonal Antibodies.The AAPS journal · 2023Article
- Modeling Blood-Brain Barrier Permeability to Solutes and Drugs In Vivo.Pharmaceutics · 2022Review
- Treatment of Neuronopathic Mucopolysaccharidoses with Blood-Brain Barrier-Crossing Enzymes: Clinical Application of Receptor-Mediated Transcytosis.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
In this manuscript, we present a translational physiologically-based pharmacokinetic (PBPK) model to characterize receptor-mediated transcytosis (RMT) of anti-transferrin receptor (TfR) monoclonal antibodies (mAbs) in the central nervous system (CNS). The model accounts for the state-of-the-art knowledge of the brain's anatomy and physiology, and physiological parameters were fixed according to different species. By estimating a few parameters associated with the TfR concentration, the TfR turnover, and the internalization rate, the model simultaneously characterizes plasma, whole brain, interstitial fluid (ISF), and cerebrospinal fluid (CSF) PK of unbound and bound anti-TfR mAbs with different binding affinities in mice, rats, and monkeys obtained from various literature sources within a threefold prediction error. The final PBPK model was validated using external anti-TfR mAb PK data in mice and monkeys with different affinities and doses. The simulation reasonably predicted plasma and brain PK of monovalent/bivalent anti-TfR mAbs within a threefold prediction error and characterized a bell-shaped relationship between the brain ISF/plasma AUC ratio and the K
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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.