The highly permeable blood-brain barrier: an evaluation of current opinions about brain uptake capacity

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 A(2), molecular weight > 1,000 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.