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- W2040972896 endingPage "26" @default.
- W2040972896 startingPage "15" @default.
- W2040972896 abstract "The extent to which a substance in the circulation gains access to the CNS needs to be determined for potential neuropharmaceuticals as well as for drug candidates with primary targets in the periphery. Characteristics of thein vivo methods, ranging from classical pharmacokinetic techniques (intravenous administration and tissue sampling) over brain perfusions to microdialysis and imaging techniques, are highlighted.In vivo measurements remain unmatched with respect to sensitivity and for the characterization of carrier-mediated uptake, receptor-mediated transport, and active efflux. Isolated microvessels are valuable tools for molecular characterization of transporters. Endothelial cell culture models of the blood-brain barrier (BBB) are pursued asin vitro systems suitable for screening procedures. Recent applications of conditionally immortalized cell lines indicate that a particular weakness of culture models because of downregulation of BBB-specific transporter systems can be overcome.In silico approaches are being developed with the goal of predicting brain uptake from molecular structure at early stages of drug development. Currently, the predictive capability is limited to passive, diffusional uptake and predominantly relies on few molecular descriptors related to lipophilicity, hydrogen bonding capacity, charge, and molecular weight. A caveat with most present strategies is their reliance on surrogates of BBB transport, like CNS activity/inactivity or brain-to-blood partitioning rather than actual BBB permeability data." @default.
- W2040972896 created "2016-06-24" @default.
- W2040972896 creator A5082705765 @default.
- W2040972896 date "2005-01-01" @default.
- W2040972896 modified "2023-10-07" @default.
- W2040972896 title "How to measure drug transport across the blood-brain barrier" @default.
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