THERMODYNAMIC ASPECTS OF HYDROPHOBICITY AND THE BLOOD-BRAIN-BARRIER PERMEABILITY STUDIES WITH A GEL-FILTRATION CHROMATOGRAPHY

It has been said that the selective permeability across the blood-brai n barrier depends on several physicochemical properties of drugs such as hydrophobicity, molecular weight, and hydrogen-bonding potential. I n order to investigate quantitatively the relationship between the blo od-brain barrier permeability and the hydrophobicity of drugs, we have measured the micelle/water partition properties (P-mic) by the MLC (m icellar liquid chromatography) method using a gel filtration version a nd compared with the blood-brain barrier permeability. The thermodynam ic aspects of partition were derived by separating the micelle/water p artition coefficient (log P-mic) into the enthalpy term P-H and the en tropy term P-S. It was found that the P-H shows a good correlation to the permeability, although log P-mic fails to do so. The result means that P-H, which is easily obtained from the in vitro experiment, can b e used as an excellent standard in discussing the transport phenomena through the blood-brain barrier.