Quantitative brain microdialysls study on the mechanism of quinolones distribution in the central nervous system

Tsuyoshi Ooie, Tetsuya Terasaki, Hiroshi Suzuki, Yuichi Sugiyama

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

Brain interstitial fluid (ISF) concentrations, which regulate the toxicodynamic effect of quinolone antimicrobial agents (quinolones) in the central nervous system, have been determined for norfloxacin, ofloxacin, fleroxacin, and pefloxacin using a quantitative brain microdialysis technique. Steady-state brain ISF concentrations of the quinolones were 7-30 times lower than the unbound serum concentrations due to restricted distribution in the brain. Cerebrospinal fluid concentrations of the quinolones were approximately twice as high as the brain ISF concentrations, except for norfloxacin. Thus, it seems that an active efflux transport system across the blood-brain barrier is responsible for maintaining brain ISF concentrations lower than unbound serum concentrations at steady-state. A good correlation was observed for norfloxacin, ofloxacin, fleroxacin, and pefloxacin between brain ISF concentrations and total brain concentrations. Moreover, a relatively small difference was observed among the quinolones for the in vitro brain slice-to-medium concentration ratio, compared with an 11- fold difference in the in vivo brain-to-unbound serum concentration ratio after intravenous infusion. These results indicate that the different quinolones studied all exhibit similar apparent binding and/or uptake by brain parenchyma, with an average brain ISF-to-total brain concentration ratio of 0.688.

Original languageEnglish
Pages (from-to)784-789
Number of pages6
JournalDrug Metabolism and Disposition
Volume25
Issue number7
Publication statusPublished - 1997 Jul 1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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