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Journal of Pharmacology And Experimental Therapeutics, Vol. 125, Issue 3, 185-193, 1959
Copyright © 1959 by American Society for Pharmacology and Experimental Therapeutics

DISTRIBUTION OF DRUGS BETWEEN BLOOD AND CEREBROSPINAL FLUID: GENERAL METHODOLOGY AND EFFECT OF pH GRADIENTS

David P. Rall 1, James R. Stabenau 1, Charles G. Zubrod 1, and James Gaskins 1

1 National Cancer Institute, National Institutes of Health, Bethesda, Maryland

A standardized technique has been developed to study the distribution of drugs between blood and cerebrospinal fluid in the dog. The two parameters which describe drug distribution between blood and CSF are the steady state CSF/ plasma drug ratio (RCSF) and the rate of approach to this steady state ratio (k).

Certain drugs which are weak organic electrolytes have been studied in this manner to determine their distribution between blood and CSF. These drugs appear to pass from blood to CSF to reach a steady state ratio (RCSF) characteristic of each drug according to its pKa and the existance of a normal pH gradient between blood and CSF.

Under conditions of various acutely produced pH gradients the drug distribution ratio of certain of these drugs can be significantly and predictably altered. The explanation is based on the hypothesis that the membrane separating the blood and CSF is permeable only to the unionized form of these compounds, and the pKa of these compounds falls in the range where a pH gradient favors an unequal distribution of total drug.

Submitted on October 9, 1958






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Copyright © 1959 by the American Society for Pharmacology and Experimental Therapeutics.