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JAC Advance Access published online on April 11, 2005
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dki075
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© The Author 2005. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oupjournals.org 
Received November 16, 2004
Revised January 21, 2005
Accepted January 26, 2005

Brief report

Uptake and intracellular activity of voriconazole in human polymorphonuclear leucocytes

Sofía Ballesta 1*, Isabel García 1, Evelio J. Perea 1, and Alvaro Pascual 1

1 Department of Microbiology, School of Medicine, University of Seville, Spain

* To whom correspondence should be addressed.
Sofía Ballesta, E-mail: mudarra{at}us.es


  Abstract

Objectives: The intracellular penetration of voriconazole into human polymorphonuclear leucocytes (PMNs) and its intracellular activity against Candida spp. were evaluated.

Methods: The intracellular penetration of voriconazole into PMNs was evaluated by a radiometric assay. The effect of cell viability, environmental conditions, metabolic inhibitors and membrane stimulation was also studied. The intracellular activity was determined by incubation of PMNs containing intracellular blastospores in the presence of voriconazole for 3 h.

Results: The uptake of voriconazole by PMNs was rapid and not saturable. The cellular to extracellular concentration (C/E) ratio for voriconazole was 8.5±1.3. Voriconazole was rapidly released from loaded PMNs. The uptake of voriconazole was not affected by environmental temperature and cell viability. Neither the external pH nor the metabolic inhibitors affected the uptake of voriconazole. The ingestion of opsonized zymosan, but not of opsonized Candida spp., significantly decreased the levels of PMN-associated voriconazole. At the extracellular concentrations evaluated, voriconazole did not affect the intracellular survival of Candida.

Conclusions: Voriconazole reached high intracellular concentrations within human PMNs. The uptake was rapid and not saturable but it did not affect the intracellular killing of Candida spp.

Keywords: Candida; azoles; accumulation.
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