PT  - JOURNAL ARTICLE
AU  - Bernard B. Brodie
AU  - Hehmann Kurz
AU  - Lewis S. Schanker
TI  - THE IMPORTANCE OF DISSOCIATION CONSTANT AND LIPID-SOLUBILITY IN INFLUENCING THE PASSAGE OF DRUGS INTO THE CEREBROSPINAL FLUID
DP  - 1960 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 20--25
VI  - 130
IP  - 1
4099  - http://jpet.aspetjournals.org/content/130/1/20.short
4100  - http://jpet.aspetjournals.org/content/130/1/20.full
SO  - J Pharmacol Exp Ther1960 Sep 01; 130
AB  - 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.