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  • Title: Challenges for blood-brain barrier (BBB) screening.
    Author: Jeffrey P, Summerfield SG.
    Journal: Xenobiotica; 2007; 37(10-11):1135-51. PubMed ID: 17968740.
    Abstract:
    Whilst blood-brain barrier permeability is an important determinant in achieving efficacious central nervous system drug concentrations, it should not be viewed or measured in isolation. Recent studies have highlighted the need for an integrated approach where optimal central nervous system penetration is achieved through the correct balance of permeability, a low potential for active efflux, and the appropriate physicochemical properties that allow for drug partitioning and distribution into brain tissue. Integrating data from permeability studies performed incorporating an assessment of active efflux by P-glycoprotein in combination with drug-free fraction measurements in blood and brain has furthered the understanding of the impact of the blood-brain barrier on central nervous system uptake and the underlying physicochemical properties that contribute to central nervous system drug disposition. This approach moves away from screening and ranking compounds in assays designed to measure or predict central nervous system penetration in the somewhat arbitrary units of brain-blood (or plasma) ratios.
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