title: Population pharmacokinetics of moxifloxacin in plasma and bronchial secretions in patients with severe bronchopneumonia.
abstract: OBJECTIVE
  Our objective was to construct a population pharmacokinetic model for moxifloxacin disposition in plasma and bronchial secretions in patients with severe bronchopneumonia who were mechanically ventilated.
  
  
  METHODS
  Seventeen patients receiving 400 mg moxifloxacin intravenously daily were enrolled in this multicenter, prospective, open-label study. Blood and bronchial samples were collected on days 1 and 4. The population pharmacokinetic modeling was performed with NONMEM.
  
  
  RESULTS
  Moxifloxacin rapidly appeared in bronchial secretions and reached maximum concentrations within 1 to 2 hours. The concentrations achieved in plasma and bronchial secretions showed parallel profiles versus time on days 1 and 4. The pharmacokinetics was best described by a 2-compartment model with a link to bronchial secretions. The population pharmacokinetic parameters were as follows (given as estimate with percent interindividual variability in parentheses except where otherwise indicated): clearance, 14.3 L/h (25%); central distribution volume, 62.9 L (14%); intercompartmental clearance, 27.2 L/h (36%); peripheral distribution volume; 71 L (32%); fraction of moxifloxacin clearance to bronchial secretions, 0.11 (range, 0.06-0.16); and elimination rate constant for bronchial secretions, 1.7 h(-1) (40%). The plasma terminal half-life was 6.7 hours. The bronchial-to-plasma exposure ratio was 1.0 (range, 0.6-2.0). With a conservative 90% minimum inhibitory concentration (MIC(90)) of 0.25 mg/L, the maximum concentration/MIC(90) ratios were higher than 10 and the area under the curve/MIC(90) ratios were roughly 100 for plasma and bronchial secretions.
  
  
  CONCLUSIONS
  This study showed the fast diffusion of moxifloxacin into the lungs in ventilated patients with severe respiratory infection. The bronchial secretions reached bactericidal levels for common germs found in respiratory tract infections.
authors.affiliation: Department of Pharmacology, CHU Timone, Marseille, France. nicolas.simon@medecine.univ-mrs.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Simon
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Sampol
authors.forename: Jacques
authors.initials: J
authors.lastname: Albanese
authors.forename: Claude
authors.initials: C
authors.lastname: Martin
authors.forename: Pierre
authors.initials: P
authors.lastname: Arvis
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Bruno
authors.initials: B
authors.lastname: Lacarelle
authors.forename: Bernard
authors.initials: B
authors.lastname: Bruguerolle
mesh_terms: D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D001372:Aza Compounds; D001980:Bronchi / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001996:Bronchopneumonia / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D000077266:Moxifloxacin; D011446:Prospective Studies; D011804:Quinolines; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin