Journal
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Volume 322, Issue 1, Pages 205-213Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.107.121525
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The dispositions of 50 marketed central nervous system ( CNS) drugs into the brain have been examined in terms of their rat in situ ( P) and in vitro apparent membrane permeability ( P app) alongside lipophilicity and free fraction in rat brain tissue. The inter- relationship between these parameters highlights that both permeability and brain tissue binding influence the uptake of drugs into the CNS. Hydrophilic compounds characterized by low brain tissue binding display a strong correlation ( R-2 = 0.82) between P and P-app, whereas the uptake of more lipophilic compounds seems to be influenced by both P-app and brain free fraction. A nonlinear relationship is observed between logP(oct) and P over the 6 orders of magnitude range in lipophilicity studied. These findings corroborate recent reports in the literature that brain penetration is a function of both rate and extent of drug uptake into the CNS.
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