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Article
Translational two-pore PBPK model to characterize whole-body disposition of different-size endogenous and exogenous proteins
Two-pore physiologically based pharmacokinetic (PBPK) modeling has demonstrated its potential in describing the pharmacokinetics (PK) of different-size proteins. However, all existing two-pore models lack eith...
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Article
Investigation of Antibody Pharmacokinetics in the Brain Following Intra-CNS Administration and Development of PBPK Model to Characterize the Data
Despite the promising potential of direct central nervous system (CNS) antibody administration to enhance brain exposure, there remains a significant gap in understanding the disposition of antibodies followin...
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Article
Expansion of platform physiologically-based pharmacokinetic model for monoclonal antibodies towards different preclinical species: cats, sheep, and dogs
Monoclonal antibodies (mAbs) are becoming an important therapeutic option in veterinary medicine, and understanding the pharmacokinetic (PK) of mAbs in higher-order animal species is also important for human d...
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Article
Assessment of AAV9 distribution and transduction in rats after administration through Intrastriatal, Intracisterna magna and Lumbar Intrathecal routes
Challenges in obtaining efficient transduction of brain and spinal cord following systemic AAV delivery have led to alternative administration routes being used in clinical trials that directly infuse the viru...
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Article
Calibration of cohesive parameters for fracture test simulations of sub-sized bend specimens of AM steels
Crack extensions in sub-sized side-grooved bend specimens of AM steels are examined with changing cohesive parameters. Two-dimensional FE analyses are first conducted to simulate crack extensions by nodal rele...
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Article
PBPK model for antibody disposition in mouse brain: validation using large-pore microdialysis data
The objective of this manuscript was to validate a physiologically-based pharmacokinetic (PBPK) model developed to characterize brain pharmacokinetics (PK) of monoclonal antibodies (mAbs) using novel large-por...
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Article
Towards a translational physiologically-based pharmacokinetic (PBPK) model for receptor-mediated transcytosis of anti-transferrin receptor monoclonal antibodies in the central nervous system
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 (...
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Article
Correction: Effect of the Size of Protein Therapeutics on Brain Pharmacokinetics Following Systematic Administration
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Article
Effect of the Size of Protein Therapeutics on Brain Pharmacokinetics Following Systematic Administration
Here, we have investigated the effect of size of protein therapeutics on brain pharmacokinetics (PK) following systemic administration in rats. All tested proteins were derived from trastuzumab that do not bin...
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Article
Open AccessAlgorithmic multiscale analysis for the FcRn mediated regulation of antibody PK in human
A demonstration is provided on how algorithmic asymptotic analysis of multi-scale pharmacokinetics (PK) systems can provide (1) system level understanding and (2) predictions on the response of the model when ...
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Protocol
Determination of ADC Cytotoxicity in Immortalized Human Cell Lines
Cytotoxicity assays are a necessary first step to triage ADC molecules before moving them forward to relatively time-consuming and expensive in vivo studies. When cells are exposed to ADC molecules, antigen ex...
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Article
A translational platform PBPK model for antibody disposition in the brain
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 m...