PT  - JOURNAL ARTICLE
AU  - Tsuyoshi Ooie
AU  - Tetsuya Terasaki
AU  - Hiroshi Suzuki
AU  - Yuichi Sugiyama
TI  - Quantitative Brain Microdialysis Study on the Mechanism of Quinolones Distribution in the Central Nervous System
DP  - 1997 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 784--0789
VI  - 25
IP  - 7
4099  - http://dmd.aspetjournals.org/content/25/7/784.short
4100  - http://dmd.aspetjournals.org/content/25/7/784.full
SO  - Drug Metab Dispos1997 Jul 01; 25
AB  - 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 thein vitro brain slice-to-medium concentration ratio, compared with an 11-fold difference in the in vivobrain-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. The American Society for Pharmacology and Experimental Therapeutics