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• W2000820979 abstract "A wide variety of models have been developed over the years to predict blood–brain barrier (BBB) penetration, most of them have focussed on predicting total concentrations of drug and then expressing this as a brain:blood (or plasma) ratio. This approach is somewhat flawed and fails to address the critical issue of understanding the relationship between access of free drug to the requisite site of action. In this short review, we highlight the need for an integrated approach and whilst blood–brain barrier permeability is an important determinant in achieving efficacious CNS drug concentrations it should not be viewed or measured in isolation. Optimal CNS 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. Such an approach should enhance and accelerate our understanding and ability to predict CNS efficacy in terms of free drug concentrations and the rate at which they are achieved." @default.
• W2000820979 created "2016-06-24" @default.
• W2000820979 creator A5009201537 @default.
• W2000820979 creator A5011157656 @default.
• W2000820979 date "2010-01-01" @default.
• W2000820979 modified "2023-10-01" @default.
• W2000820979 title "Assessment of the blood–brain barrier in CNS drug discovery" @default.
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• W2000820979 doi "https://doi.org/10.1016/j.nbd.2009.07.033" @default.
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