ArticleJournal of pharmacokinetics and pharmacodynamics2019
A translational platform PBPK model for antibody disposition in the brain.
Article in Journal of pharmacokinetics and pharmacodynamics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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.
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Who cites it
54 citing papers in PubMed, 77 citations in OpenAlex.
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- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Advances in Machine Learning-Enhanced PBPK Models for Brain-Targeted Drug Delivery via Nanocarriers: A Comprehensive Review.Journal of functional biomaterials · 2026Review
- QSP model for AAV-mediated antibody delivery in rat brain.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Differential expression of monoclonal antibody in rat brain following systemic and local administration of AAV.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Development of a Dual-Isotope Imaging Technique for Simultaneous Quantification and Evaluation of Biodistribution of Antibodies Using "XCam-CdTe".Pharmaceutical research · 2026Article
- Integrating In-vitro Permeability Assays within PBPK Modeling to Predict CNS Distribution of Standard and Engineered Antibodies.The AAPS journal · 2026Article
- Safety, tolerability and biomarker results of bepranemab in participants with progressive supranuclear palsy: a randomised, multicentre, double-blind, placebo-controlled, phase 1b trial.BMJ neurology open · 2026Article
- The role for artificial intelligence in identifying combination therapies for Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
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- Modernizing Preclinical Drug Development: The Role of New Approach Methodologies.ACS pharmacology & translational science · 2025Review
- Synaptotoxic effects of extracellular tau are mediated by its microtubule-binding region.Acta neuropathologica · 2025Article
- A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Effect of FcRn Binding on Monoclonal Antibody Disposition in the Brain.The AAPS journal · 2025Article
- Intrathecal administration of Anti-Nogo-A antibody in macaque monkeys: Pharmacokinetics, tissue penetration and target interaction.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Predicting seizure liability of small molecules using an in vitro multi-electrode array based assay coupled with modeling of brain disposition.Current research in toxicology · 2025Article
- Modeling biomarker kinetics of Aβ levels in serum following blast.Frontiers in neurology · 2025Article
- Expansion of platform physiologically-based pharmacokinetic model for monoclonal antibodies towards different preclinical species: cats, sheep, and dogs.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Translational physiologically-based pharmacokinetic model for ocular disposition of monoclonal antibodies.Journal of pharmacokinetics and pharmacodynamics · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
In this manuscript, we have presented the development of a novel platform physiologically-based pharmacokinetic (PBPK) model to characterize brain disposition of mAbs in the mouse, rat, monkey and human. The model accounts for known anatomy and physiology of the brain, including the presence of distinct blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier. CSF and interstitial fluid turnover, and FcRn mediated transport of mAbs are accounted for. The model was first used to characterize published and in-house pharmacokinetic (PK) data on the disposition of mAbs in rat brain, including the data on PK of mAb in different regions of brain determined using microdialysis. Majority of model parameters were fixed based on literature reported values, and only 3 parameters were estimated using rat data. The rat PBPK model was translated to mouse, monkey, and human, simply by changing the values of physiological parameters corresponding to each species. The translated PBPK models were validated by a priori predicting brain PK of mAbs in all three species, and comparing predicted exposures with observed data. The platform PBPK model was able to a priori predict all the validation PK profiles reasonably well (within threefold), without estimating any parameters. As such, the platform PBPK model presented here provides an unprecedented quantitative tool for prediction of mAb PK at the site-of-action in the brain, and preclinical-to-clinical translation of mAbs being developed against central nervous system (CNS) disorders. The proposed model can be further expanded to account for target engagement, disease pathophysiology, and novel mechanisms, to support discovery and development of novel CNS targeting mAbs.
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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.