DMD Noab BioDiscoveries - Shaping Drug Discovery

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ooie, T.
Right arrow Articles by Sugiyama, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ooie, T.
Right arrow Articles by Sugiyama, Y.

0090-9556/97/2507-0784-0789$02.00/0
DRUG METABOLISM AND DISPOSITION
Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics
Vol. 25, No. 7

Quantitative Brain Microdialysis Study on the Mechanism of Quinolones Distribution in the Central Nervous System

Tsuyoshi Ooie,1 Tetsuya Terasaki,2 Hiroshi Suzuki, and Yuichi Sugiyama

Faculty of Pharmaceutical Sciences, The University of Tokyo

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.

Copyright © 1997 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
T. Ando, H. Kusuhara, G. Merino, A. I. Alvarez, A. H. Schinkel, and Y. Sugiyama
Involvement of Breast Cancer Resistance Protein (ABCG2) in the Biliary Excretion Mechanism of Fluoroquinolones
Drug Metab. Dispos., October 1, 2007; 35(10): 1873 - 1879.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
M. Friden, A. Gupta, M. Antonsson, U. Bredberg, and M. Hammarlund-Udenaes
In Vitro Methods for Estimating Unbound Drug Concentrations in the Brain Interstitial and Intracellular Fluids
Drug Metab. Dispos., September 1, 2007; 35(9): 1711 - 1719.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. Becker and X. Liu
EVALUATION OF THE UTILITY OF BRAIN SLICE METHODS TO STUDY BRAIN PENETRATION
Drug Metab. Dispos., May 1, 2006; 34(5): 855 - 861.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
H. Sasabe, Y. Kato, T. Suzuki, M. Itose, G. Miyamoto, and Y. Sugiyama
Differential Involvement of Multidrug Resistance-Associated Protein 1 and P-Glycoprotein in Tissue Distribution and Excretion of Grepafloxacin in Mice
J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 648 - 655.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
M. Muller, A. dela Pena, and H. Derendorf
Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Distribution in Tissue
Antimicrob. Agents Chemother., May 1, 2004; 48(5): 1441 - 1453.
[Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
I. Tamai, J. Yamashita, Y. Kido, A. Ohnari, Y. Sai, Y. Shima, K. Naruhashi, S. Koizumi, and A. Tsuji
Limited Distribution of New Quinolone Antibacterial Agents into Brain Caused by Multiple Efflux Transporters at the Blood-Brain Barrier
J. Pharmacol. Exp. Ther., October 1, 2000; 295(1): 146 - 152.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Murata, I. Tamai, H. Kato, O. Nagata, H. Kato, and A. Tsuji
Efflux Transport of a New Quinolone Antibacterial Agent, HSR-903, across the Blood-Brain Barrier
J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 51 - 57.
[Abstract] [Full Text]

Home page
 Antimicrob. Agents Chemother.Home page
C. Østergaard, T. Klitmøller Sørensen, J. Dahl Knudsen, and N. Frimodt-Møller
Evaluation of Moxifloxacin, a New 8-Methoxyquinolone, for Treatment of Meningitis Caused by a PenicillinResistant Pneumococcus in Rabbits
Antimicrob. Agents Chemother., July 1, 1998; 42(7): 1706 - 1712.
[Abstract] [Full Text]

Home page
 J. Pharmacol. Exp. Ther.Home page
T. Ooie, T. Terasaki, H. Suzuki, and Y. Sugiyama
Kinetic Evidence for Active Efflux Transport across the Blood-Brain Barrier of Quinolone Antibiotics
J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 293 - 304.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.