Journal
DRUG DISCOVERY TODAY
Volume 12, Issue 23-24, Pages 1076-1082Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2007.10.005
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The blood-brain barrier is often perceived as relatively impermeable, and various cut-off values for zero or limited brain permeability have been suggested. The validity of these values has been evaluated in this review. The barrier appears to have a very high permeability and absorptive capacity: sufficient to absorb compounds with polar surface area >270 angstrom(2), molecular weight >1000 Da, log D < -3.5 and equilibrium brain-to-blood concentration ratio <0.01 well. Sufficient intestinal uptake indicates good passive brain uptake potential. The uptake is potentially more sensitive to involvement and changes of active transport than in the intestines. A physiologically based in vitro-in vivo method for prediction of brain uptake is presented.
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