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This is not an anatomical barrier as such, rather a combination of the tight junctions between endothelial cells of brain capillaries and the close association of glial cells with the outside of the capillaries. This arrangement makes diffusion of lipid-soluble drugs into the brain difficult and diffusion of water-soluble drugs almost impossible. A large number of drugs have a high affinity for albumin and other plasma proteins.
Binding to plasma protein inhibits distribution outside the blood since only unbound drug will be further distributed. Plasma protein binding therefore reduces active drug concentration and ultimate response to the drug.