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Population pharmacokinetics of moxifloxacin in plasma and bronchial secretions in patients with severe bronchopneumonia
Author(s) -
Simon Nicolas,
Sampol Emmanuelle,
Albanese Jacques,
Martin Claude,
Arvis Pierre,
Urien Saîk,
Lacarelle Bruno,
Bruguerolle Bernard
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(03)00201-7
Subject(s) - bronchopneumonia , pharmacokinetics , moxifloxacin , medicine , population pharmacokinetics , population , pharmacology , antibiotics , microbiology and biotechnology , pediatrics , biology , environmental health
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. Clinical Pharmacology & Therapeutics (2003) 74 , 353–363; doi: 10.1016/S0009‐9236(03)00201‐7