Abstract
Summary
Lipid/water partition coefficients of 19 radiolabeled drugs were correlated with uptake by brain during a single microcirculatory passage following carotid arterial injection. Uptake was measured relative to a simultaneously injected diffusible reference. When the lipid/ water partition coefficient was greater than about 0.03 a substantial fraction of the drug penetrated the blood-brain barrier and for most drugs above this range, uptake was essentially complete. These data suggest there is probably little reason to greatly exceed this degree of lipid solubility when designing drugs for blood-brain barrier penetration and central nervous system effects.
Valuable discussions with Dr. Arthur K. Cho and Dr. Jared M. Diamond are acknowledged. Helpful suggestions from Mrs. Stella Z. Oldendorf were received, and technical assistance was provided by Mrs. Shigeyo Hyman and Mr. Leon Braun. Support is also acknowledged from the NIH-NINDS Project Grant No. NS 8711 and the Veterans Administration.
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