Relative hydrophobicity and lipophilicity of drugs measured by aqueous two-phase partitioning, octanol-buffer partitioning and HPLC. A simple model for predicting blood-brain distribution.
Relative hydrophobicity and lipophilicity of 63 compounds with known permeability through the blood-brain barrier (BBB) was examined by partitioning in aqueous dextran-poly(ethylene glycol) two-phase system and octanol-buffer system, and by gradient RP-HPLC at pH 7.4. Combination of the relative hydrophobicity estimates, N(CH(2)) obtained by aqueous two-phase partitioning and the lipophilicity (logD(exp) or logD(HPLC)) values obtained by the shake-flask technique or HPLC technique allows one to differentiate between compounds capable of crossing the BBB and those that cannot. A simple model for predicting blood-brain distribution is proposed.
Gulyaeva
Nellie
N
Analiza, Inc., 26101 Miles Road, Cleveland, OH 44128, USA.
Zaslavsky
Alexander
A
Lechner
Pamela
P
Chlenov
Michael
M
McConnell
Oliver
O
Chait
Arnon
A
Kipnis
Victor
V
Zaslavsky
Boris
B
D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003911:Dextrans / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D000442:Octanols / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D014867:Water / Q000737:chemistry
D003911:Dextrans; D008055:Lipids; D000442:Octanols; D004364:Pharmaceutical Preparations; D014867:Water; D011092:Polyethylene Glycols