This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
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
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Brillault, J.
Right arrow Articles by Couet, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Brillault, J.
Right arrow Articles by Couet, W.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, April 2009, p. 1457-1462, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01253-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

P-Glycoprotein-Mediated Transport of Moxifloxacin in a Calu-3 Lung Epithelial Cell Model{triangledown}

Julien Brillault,1,2 Whocely Victor De Castro,1,2 Thomas Harnois,3 Alain Kitzis,2,3,4 Jean-Christophe Olivier,1,2 and William Couet1,2,4*

INSERM, ERI-23, 40 Avenue du Recteur Pineau, Poitiers, France,1 Université de Poitiers, UFR Médecine-Pharmacie, 6 Rue de la Milétrie, Poitiers, France,2 Institut de Physiologie et de Biologie Cellulaire, CNRS UMR6187, Université de Poitiers, Poitiers, France,3 CHU Poitiers, 2 Rue de la Milétrie, Poitiers, France4

Received 19 September 2008/ Returned for modification 3 December 2008/ Accepted 17 January 2009

Moxifloxacin (MXF) is a fluoroquinolone antibiotic that is effective against respiratory infections. However, the mechanisms of MXF lung diffusion are unknown. Active transport in other tissues has been suggested for several members of the fluoroquinolone family. In this study, transport of MXF was systematically investigated across a Calu-3 lung epithelial cell model. MXF showed polarized transport, with the secretory permeability being twice as high as the absorptive permeability. The secretory permeability was concentration dependent (apparent Pmax = 13.6 x 10–6 cm·s–1; apparent Km = 147 µM), suggesting saturated transport at concentrations higher than 350 µg/ml. The P-glycoprotein inhibitor PSC-833 inhibited MXF transport in both directions, whereas probenecid, a multidrug resistance-related protein inhibitor, appeared to have no effect in the Calu-3 model. Moreover, rifampin, a known inducer of efflux transport proteins, upregulated the expression of P-glycoprotein in Calu-3 cells and enhanced MXF active transport. In conclusion, this study clearly indicates that MXF is subject to P-glycoprotein-mediated active transport in the Calu-3 model. This P-glycoprotein-dependent secretion may lead to higher MXF epithelial lining fluid concentrations than those in plasma. Furthermore, drug-drug interactions may be expected when MXF is combined with other P-glycoprotein substrates or modulators.

* Corresponding author. Mailing address: INSERM, ERI-23, Pôle Biologie Santé, 40 Avenue du Recteur Pineau, 86000 Poitiers, France. Phone: (33) 5 49 45 43 79. Fax: (33) 5 49 45 43 78. E-mail: william.couet{at}univ-poitiers.fr

{triangledown} Published ahead of print on 2 February 2009.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1457-1462, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.01253-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»