title: High extracellular levels of cefpirome in unaffected and infected lung tissue of patients.
abstract: OBJECTIVE
  the objective of the present investigation was to measure the extracellular concentrations of cefpirome in unaffected and infected lung tissue of septic patients.
  
  
  METHODS
  a single intravenous dose of 30 mg/kg total body weight of cefpirome was administered to eight patients every 12 h prior to insertion of microdialysis probes into lung tissue.
  
  
  RESULTS
  the median (minimum, maximum) peak concentration (C(max)), time to C(max) (T(max)), area under the concentration-time curve from 0 to 4 h (AUC(0-4)) and AUC(0-∞) of unbound cefpirome for unaffected lung were 48 (32, 107) mg/L, 0.83 (0.17, 3.17) h, 117 (60, 177) mg · h/L and 182 (80, 382) mg · h/L, respectively. The corresponding values for infected lung tissue were 45 (6, 122) mg/L, 1.17 (0.83, 2.83) h, 92 (17, 253) mg · h/L and 206 (49, 379) mg · h/L, respectively. The median apparent terminal elimination half-lives (t(&frac12;z)) of cefpirome were 2.61, 3.05 and 3.39 h for plasma, unaffected lung and infected lung, respectively. The median ratios of the AUC(0)(-∞) for lung to the AUC(0)(-∞) for plasma were 0.63 (0.19, 1.55) and 0.46 (0.32, 0.98) for unaffected and infected lung, respectively.
  
  
  CONCLUSIONS
  we provide strong evidence that cefpirome penetrates effectively into the extracellular space fluid of lung tissue. Under steady-state conditions, the median concentrations of cefpirome in plasma, unaffected lung and infected lung exceeded the MICs of the majority of relevant bacteria over the entire dosing interval of up to 12 h after intravenous administration of a dose of 30 mg/kg total body weight.
authors.affiliation: Division of Thoracic and Hyperbaric Surgery, Medical University of Graz, Graz, Austria.
authors.forename: Jörg
authors.initials: J
authors.lastname: Lindenmann
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Kugler
authors.forename: Veronika
authors.initials: V
authors.lastname: Matzi
authors.forename: Christian
authors.initials: C
authors.lastname: Porubsky
authors.forename: Alfred
authors.initials: A
authors.lastname: Maier
authors.forename: Peter
authors.initials: P
authors.lastname: Dittrich
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Graninger
authors.forename: Freyja M
authors.initials: FM
authors.lastname: Smolle-Jüttner
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008168:Lung / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D000097572:Cefpirome
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D000097572:Cefpirome