Abstract

Studies with 14 compounds indicate that the passage of drugs into cerebrospinal fluid (CSF) is governed mainly by two physical properties: the degree of ionization of the drug; and the lipidsolubility of the undissociated drug molecule. Lipid-solubility is the rate-limiting factor with drugs that are mainly undissociated at pH 7.4; these compounds penetrate the blood-CSF barrier at rates roughly related to the lipid/water partition coefficient of the undissociated molecules. The concentration of undissociated molecules is the rate-limiting factor with compounds that are highly ionized; these drugs enter the CSF at rates roughly parallel to the proportion of drug undissociated at pH 7.4.

The results have been obtained with such a large number of compounds of diverse structures and physical properties that they add considerable validity to the assumption that the blood-CSF barrier behaves as an inert lipoid membrane to most foreign organic compounds.