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Microdialysis of Ethanol During Operant Ethanol Self-administration and Ethanol Determination by Gas Chromatography
Published on: September 5, 2012
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Antibody pharmacokinetics in rat brain determined using microdialysis
Hsueh-Yuan Chang1, Kasey Morrow1, Emily Bonacquisti1
1a Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences , The State University of New York at Buffalo , Buffalo, NY , USA.
Mabs
|June 27, 2018
Summary
This study used microdialysis to measure antibody levels in various rat brain regions. Cerebrospinal fluid antibody concentrations varied by collection site, and did not reflect brain parenchyma levels, informing antibody drug development for CNS disorders.
Area of Science:
- Neuroscience
- Pharmacology
- Biotechnology
Background:
- Antibody distribution in the brain is crucial for treating central nervous system (CNS) disorders.
- Understanding antibody pharmacokinetics within different brain regions is essential for optimizing therapeutic strategies.
Purpose of the Study:
- To investigate antibody pharmacokinetics in distinct rat brain regions using microdialysis.
- To compare antibody concentrations in cerebrospinal fluid (CSF) and brain parenchyma.
- To explore antibody disposition in both steady-state and dynamic settings.
Main Methods:
- Microdialysis was employed to collect samples from the striatum (ST), lateral ventricle (LV), and cisterna magna (CM) in rats.
- Both endogenous IgG and exogenously administered trastuzumab were analyzed.
- Plasma and brain homogenate concentrations were measured for comprehensive pharmacokinetic analysis.
Main Results:
- Antibody concentrations in CSF varied significantly between collection sites (CM > LV).
- CSF antibody levels did not accurately represent concentrations within brain parenchyma (e.g., ST).
- Elimination and transport rates differed across brain regions, with slower kinetics observed in CM and ST.
Conclusions:
- Microdialysis provides unprecedented insight into regional brain antibody disposition.
- Findings highlight the importance of site-specific measurements for accurate pharmacokinetic assessment.
- This research can guide the design of improved antibody therapeutics for CNS diseases.
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