title: Pharmacokinetics of moxifloxacin and high-dose levofloxacin in severe lower respiratory tract infections.
abstract: This study evaluated the pharmacokinetics of intravenous moxifloxacin 400 mg once and levofloxacin 500 mg twice daily in patients with lower respiratory tract infections (LRTIs) and assessed their pharmacodynamic adequacy against common respiratory pathogens. Eighteen patients with LRTIs hospitalised in general wards were included. Serial blood samples were obtained at steady state and concentrations were determined using HPLC. Pharmacokinetic variables were estimated by a two-compartment model. The characteristic pharmacodynamic parameter for fluoroquinolones (AUC(0-24)/MIC) was calculated. Peak and trough concentrations were, respectively, 4.81 ± 1.03 and 0.59 ± 1.13 mg/L for moxifloxacin and 6.42 ± 1.08 and 0.79 ± 0.39 mg/L for levofloxacin. Pharmacokinetic data for moxifloxacin and levofloxacin, respectively, were: CL, 10.27 ± 1.24 and 22.66 ± 6.62 L/h; t1/2, 13.43 ± 5.12 and 6.75 ± 1.34 h; Vss, 163.03 ± 53.88 and 170.73 ± 39.59 L; and AUC(0-24), 39.38 ±5.28 and 47.06 ± 14.09 mg·h/L. The pharmacodynamic target was attained in all patients by both antibiotics against the majority of respiratory pathogens. Moxifloxacin proved to be pharmacodynamically efficacious against Gram-positive bacteria with MICs ≤ 0.79 mg/L and Gram-negative bacteria with MICs ≤ 0.32 mg/L. These MIC thresholds for levofloxacin were 1.1 mg/L and 0.38 mg/L, respectively. Moxifloxacin and high-dose levofloxacin show a favourable pharmacokinetic profile in plasma of patients with severe LRTIs, without significant interpatient variability. They ensure optimal pharmacodynamic exposure against the majority of microbes involved in these infections. However, the predicted efficacy against Gram-negative bacteria with MICs ≥ 0.5 mg/L appears to be low.
authors.affiliation: A' Intensive Care Unit, G. Papanikolaou Hospital, Thessaloniki, Greece.
authors.forename: Paschalina
authors.initials: P
authors.lastname: Kontou
authors.forename: Katerina
authors.initials: K
authors.lastname: Manika
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Chatzika
authors.forename: Maria
authors.initials: M
authors.lastname: Papaioannou
authors.forename: Maria
authors.initials: M
authors.lastname: Sionidou
authors.forename: Georgia
authors.initials: G
authors.lastname: Pitsiou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kioumis
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001372:Aza Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D064704:Levofloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012141:Respiratory Tract Infections / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D000077266:Moxifloxacin
keywords: Fluoroquinolones; Pharmacokinetics; Respiratory tract infections