title: Pharmacokinetics of ciprofloxacin and its penetration into bronchial secretions of mechanically ventilated patients with chronic obstructive pulmonary disease.
abstract: We evaluated the pharmacokinetic profile of ciprofloxacin and its penetration into bronchial secretions of critically ill patients with chronic obstructive pulmonary disease (COPD). Twenty-five mechanically ventilated patients with severe COPD who were suffering from an acute, infectious exacerbation were included in this prospective, open-label study. All subjects received a 1-hour intravenous infusion of 400 mg ciprofloxacin every 8 h. Serial blood and bronchial secretion samples were obtained at steady state, and concentrations were determined using high-performance liquid chromatography. The pharmacodynamic parameters that are associated with the efficacy of fluoroquinolones against Gram-negative pathogens were also calculated. The mean peak (maximum) concentration (C(max)) and trough (minimum) concentration in plasma were 5.37 ± 1.57 and 1 ± 0.53 mg/liter, respectively. Mean values for volume of distribution, clearance, half-life, and area under the curve from 0 to 24 h (AUC(0-24)) were 169.87 ± 84.11 liters, 26.96 ± 8.86 liters/h, 5.35 ± 2.21 h, and 47.41 ± 17.02 mg · h/liter, respectively. In bronchial secretions, a mean C(max) of 3.08 ± 1.21 mg/liter was achieved in 3.12 ± 1.01 h, and the penetration ratio was 1.16 ± 0.59. The target of AUC(0-24)/MIC of ≥125 was attained in all patients, in the majority of them (76%), and in none at MICs of 0.125, 0.25, and 1 μg/ml, respectively. Slightly better results were obtained for the ratio C(max)/MIC of ≥10. In conclusion, ciprofloxacin demonstrates excellent penetration into bronchial secretions. There is wide interindividual variability in its pharmacokinetic parameters in critically ill COPD patients and inadequate pharmacodynamic exposure against bacteria with MICs of ≥0.5 μg/ml.
authors.affiliation: A'Intensive Care Unit, G. Papanikolaou Hospital, Exohi, Thessaloniki 57010, Greece. elikont@yahoo.gr
authors.forename: Paschalina
authors.initials: P
authors.lastname: Kontou
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Chatzika
authors.forename: Georgia
authors.initials: G
authors.lastname: Pitsiou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Stanopoulos
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Argyropoulou-Pataka
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kioumis
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001980:Bronchi / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000627:therapeutic use*; D016638:Critical Illness; D024841:Fluoroquinolones / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000382:microbiology* / Q000628:therapy*; D012121:Respiration, Artificial
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin