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.
Clinical Pharmacology, AstraZeneca R&D Södertälje, S-151 85 Södertälje, Sweden. urban.fagerholm@astrazeneca.com
Urban
U
Fagerholm
D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D051381:Rats
D004364:Pharmaceutical Preparations