ArticlemAbs
Antibody pharmacokinetics in rat brain determined using microdialysis.
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Who cites it
53 citing papers in PubMed, 76 citations in OpenAlex.
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- Risk of CNS relapse following pathological complete response to neoadjuvant chemotherapy in early breast cancer.Breast cancer research and treatment · 2026Article
- Bridging the blood-brain barrier: strategies to improve delivery of biologics to tumors in the brain.Fluids and barriers of the CNS · 2026Review
- Oral Bioavailability of Monoclonal Antibody.Pharmaceutics · 2025Article
- Impact of pre-existing immunity on safety and biodistribution of a single AAV9 vector intrathecal injection in cynomolgus monkeys.Molecular therapy. Methods & clinical development · 2025Article
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- New Transferrin Receptor-Targeting Conjugate Effectively Delivers DNA to Mouse Brain.Angewandte Chemie (International ed. in English) · 2025Article
- Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- A translational physiologically-based pharmacokinetic model for MMAE-based antibody-drug conjugates.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Exploring How Antibody Format Drives Clearance from the Brain.Molecular pharmaceutics · 2024Article
- Negligible In Vitro Recovery of Macromolecules from Microdialysis Using 100 kDa Probes and Dextran in Perfusion Fluid.Neurochemical research · 2024Article
- Selective Uptake of Macromolecules to the Brain in Microfluidics and Animal Models Using the HAVN1 Peptide as a Blood-Brain Barrier Modulator.Molecular pharmaceutics · 2024Article
- Investigation of Antibody Pharmacokinetics in the Brain Following Intra-CNS Administration and Development of PBPK Model to Characterize the Data.The AAPS journal · 2024Article
- The pathogenesis of multiple sclerosis: a series of unfortunate events.Clinical and experimental immunology · 2023Article
- Enhancing Antibody Exposure in the Central Nervous System: Mechanisms of Uptake, Clearance, and Strategies for Improved Brain Delivery.Journal of nanotheranostics · 2023Article
- Immunoglobulin G is a natural oxytocin carrier which modulates oxytocin receptor signaling: relevance to aggressive behavior in humans.Discover mental health · 2023Article
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- Altered behavior, brain structure, and neurometabolites in a rat model of autism-specific maternal autoantibody exposure.Molecular psychiatry · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Here, we present the first case-study where microdialysis is used to investigate the pharmacokinetics of antibody in different regions of rat brain. Endogenous IgG was used to understand antibody disposition at steady-state and exogenously administered trastuzumab was used to understand the disposition in a dynamic setting. Microdialysis samples from the striatum (ST), lateral ventricle (LV), and cisterna magna (CM) were collected, along with plasma and brain homogenate, to comprehensively understand brain pharmacokinetics of antibodies. Antibody concentrations in cerebrospinal fluid (CSF) were found to vary based on the site-of-collection, where CM concentrations were several-fold higher than LV. In addition, antibody concentrations in CSF (CM/LV) were found to not accurately represent the concentrations of antibody inside brain parenchyma (e.g., ST). Elimination of CSF from CM was found to be slower than LV, and the entry and exit of antibody from ST was also slower. Pharmacokinetics of exogenously administered antibody revealed that the entry of antibody into LV via the blood-CSF barrier may represent an early pathway for antibody entry into the brain. Plasma concentrations of antibody were 247-667, 104-184, 165-435, and 377-909 fold higher than the antibody concentrations in LV, CM, ST, and brain homogenate. It was found that the measurement of antibody pharmacokinetics in different regions of the brain using microdialysis provides an unprecedented insight into brain disposition of antibody. This insight can help in designing better molecules, dosing regimens, and route of administration, which can in turn improve the efficacy of antibodies for central nervous system disorders.
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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.