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Brain and CSF entry of the novel non-nucleoside reverse transcriptase inhibitor, GW420867X.

Abstract
(S)-2-ethyl-7-fluoro-3-oxo-3, 4-dihydro-2H-quinoxaline-carboxylic acid isopropylester (GW420867X) inhibits HIV-1 reverse transcriptase and could be used for the treatment of HIV infection. This study quantified the movement of [14C]GW420867X into the CNS by means of a guinea-pig brain perfusion technique. Results indicated that [14C]GW420867X can enter the brain (Kin: 38.4+/-7.7 microl min(-1) g(-1)) and cerebrospinal fluid (CSF; Kin: 1.2+/-0.1 microl min(-1) g(-1)). Self-inhibition studies also suggested the presence of a saturable transport system for [14C]GW420867X at the blood-brain barrier (BBB). Thus [14C]GW420867X can enter the brain via the BBB and, compared with the blood-CSF barrier, this route is the predominant pathway for the brain entry of this drug. This would suggest that GW420867X is a promising drug for the treatment of HIV infection within the brain.
AuthorsS Thomas, L Cass, W Prince, M Segal
JournalNeuroreport (Neuroreport) Vol. 11 Issue 17 Pg. 3811-5 (Nov 27 2000) ISSN: 0959-4965 [Print] England
PMID11117496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • GW420867X
  • Quinoxalines
  • Reverse Transcriptase Inhibitors
  • Mannitol
Topics
  • Animals
  • Blood-Brain Barrier (physiology)
  • Brain (metabolism)
  • Capillaries (metabolism)
  • Chemical Phenomena
  • Chemistry, Physical
  • Guinea Pigs
  • Mannitol (pharmacokinetics)
  • Quinoxalines (cerebrospinal fluid, chemistry, pharmacokinetics)
  • Reverse Transcriptase Inhibitors (cerebrospinal fluid, pharmacokinetics)
  • Solubility

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