title: Uptake and intracellular activity of voriconazole in human polymorphonuclear leucocytes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Microbiology, School of Medicine, University of Seville, Spain. mudarra@us.es
authors.forename: Sofía
authors.initials: S
authors.lastname: Ballesta
authors.forename: Isabel
authors.initials: I
authors.lastname: García
authors.forename: Evelio J
authors.initials: EJ
authors.lastname: Perea
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual
mesh_terms: D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D002175:Candida / Q000187:drug effects*; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D014230:Triazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole