The therapeutic value of many promising drugs is diminished due to the presence of a blood-brain barrier, which possesses both structural and enzymatic components.
In addition to the permeability of a therapeutic at the BBB, which is dependent on its octanol/water partition coefficient, four additional factors codetermine the amount of an agent which enters the brain - its binding to plasma constituents, its ionization at physiologic pH, its time-dependent plasma concentration profile and cerebral blood flow, which determines the access of a drug to the cerebral vasculature. All but the latter can be manipulated by chemical modification.
For some therapeutics, simple alterations in scheduling or route of administration will elevate brain concentrations above the threshold for therapeutic action. For others, however, alternative strategies are required to optimize brain delivery. The specific approach taken depends on the agent to be delivered and the location of its target within the brain.
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