title: The ability of fluconazole to penetrate into ventilated, healthy and inflamed lung tissue in a model of severe sepsis in rats.
abstract: OBJECTIVE
  We measured the extracellular concentrations of fluconazole in lung tissue of septic and healthy rats.
  
  
  METHODS
  A single intravenous dose of 6 mg/kg total body weight of fluconazole was administered intravenously to rats following insertion of microdialysis probes into lung tissue. Another probe was inserted into skeletal muscle and served as control.
  
  
  RESULTS
  The mean peak concentration (C(max)), time to C(max), area under the concentration-versus-time curve from 0 to 6 h (fAUC(0-6)) and area under the concentration-versus-time curve from 0 to ∞ of unbound fluconazole for healthy lung were 11.0 ± 2.3 mg/l, 1.9 ± 1.5 h, 47.4 ± 8.6 mg·h/l and 233.7 ± 121.1 mg·h/l, respectively. The corresponding values for inflamed lung were 11.8 ± 1.7 mg/l, 1.5 ± 0.0 h, 52.9 ± 6.2 mg·h/l and 212.6 ± 79.7 mg·h/l, respectively. The mean apparent terminal elimination half-lives of fluconazole ranged from 12.3 to 22.4 h between compartments. The ratios of the fAUC(0-6) for lung to the fAUC(0-6) for plasma were 1.38 ± 0.39 and 1.32 ± 0.04 for healthy and inflamed lung, respectively.
  
  
  CONCLUSIONS
  We provide evidence that free fluconazole levels in plasma, the extracellular space fluid of lung tissue and skeletal muscle are almost superimposable during inflammatory and normal conditions.
authors.affiliation: J&P Medical Research Ltd., Medical University of Vienna, Vienna, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mauric
authors.forename: Christiane
authors.initials: C
authors.lastname: Thallinger
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Kugler
authors.forename: Samir M
authors.initials: SM
authors.lastname: Joukhadar
authors.forename: Florian M
authors.initials: FM
authors.lastname: Kovar
authors.forename: Karl H
authors.initials: KH
authors.lastname: Konz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graninger
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005110:Extracellular Space / Q000378:metabolism; D015725:Fluconazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D001798:Blood Proteins; D008070:Lipopolysaccharides; C440499:lipopolysaccharide, Escherichia coli O111 B4; D015725:Fluconazole