Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Marchand, S.
Right arrow Articles by Couet, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marchand, S.
Right arrow Articles by Couet, W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of Antimicrobial Chemotherapy (2001) 48, 813-820
© 2001 The British Society for Antimicrobial Chemotherapy

A pharmacokinetic/pharmacodynamic approach to show that not all fluoroquinolones exhibit similar sensitivity toward the proconvulsant effect of biphenyl acetic acid in rats

Sandrine Marchand, Claudine Pariat, Anne Boulanger, Serge Bouquet and William Couet,*

Equipe ‘Médicament et BHE’, Laboratoire de Pharmacie Galénique et de Biopharmacie, Faculté de Médecine and Pharmacie, 34 rue du Jardin des Plantes, BP 199, 86005 Poitiers Cedex, France

The proconvulsant effect of biphenyl acetic acid (BPAA) on several fluoroquinolones (FQs) was investigated in vivo, by measuring drug concentrations in the biophase at the onset of convulsions. Male Sprague–Dawley rats (n = 134) were given BPAA orally, at various doses 1 h before starting FQ infusion, which was maintained until the onset of maximal seizures, when cerebrospinal fluid (CSF) and plasma samples were collected for drug concentration determination. The FQ–BPAA interactions in the biophase (CSF) were adequately described on most occasions by an inhibitory Emax effect model with a baseline effect parameter. The efficacy of the proconvulsant effect was characterized by the ratio of the CSF concentrations of FQs at the onset of convulsant activity when BPAA was absent (CCSF0, FQs) and as BPAA CSF concentrations tended toward infinity (CCSFbase, FQs). This ratio varied from 15 for enoxacin to 1.9 for sparfloxacin. The potency of the proconvulsant effect was characterized by the CSF concentration of BPAA corresponding to a proconvulsant effect half of its maximum. This parameter varied between 0.18 ± 0.06 µmol/L with enoxacin and 15.0 ± 12.1 µmol/L with sparfloxacin. The CSF diffusion of all FQs was apparently non-linear, as well as the plasma protein binding of BPAA, complicating interpretation of plasma data. The important variability in the proconvulsant effect of BPAA demonstrated in this study between various FQs suggests that in vitro {gamma}-aminobutyric acid (GABA) binding experiments conducted in the presence of BPAA are unlikely to be good predictors of FQ convulsant risk in clinical practice.

* Corresponding author. Tel: +33-5-49-45-43-79; Fax: +33-5-49-45-43-78; E-mail: william.couet{at}univ-poitiers.fr


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.