RT Journal Article
SR Electronic
T1 THE IMPORTANCE OF DISSOCIATION CONSTANT AND LIPID-SOLUBILITY IN INFLUENCING THE PASSAGE OF DRUGS INTO THE CEREBROSPINAL FLUID
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 20
OP 25
VO 130
IS 1
A1 Bernard B. Brodie
A1 Hehmann Kurz
A1 Lewis S. Schanker
YR 1960
UL http://jpet.aspetjournals.org/content/130/1/20.abstract
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.