title: Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections.
abstract: The objective of this study was to provide a pharmacokinetic/pharmacodynamic (PK/PD) analysis of moxifloxacin in patients with diabetic foot infections (DFI). The plasma concentration-time courses were determined in 50 DFI patients on day 1 and 3 after intravenous moxifloxacin 400 mg once-daily. A two-compartment population pharmacokinetic model was developed, identifying as covariates total body weight on central and peripheral volume of distribution (V1, V2) and ideal body weight on clearance (CL), respectively. For a 70 kg patient V1 was 68.1 L (interindividual variability, CV: 27.4%), V2 44.6 L, and CL 12.1 L/h (25.6%). Simulations were performed to calculate the probability of target attainment (PTA) for Gram-positive and Gram-negative pathogens with fAUC/MIC targets of ≥30 and ≥100, respectively. PTA was 0.68-1 for susceptible (MIC ≤0.5 mg/L according to EUCAST) Gram-positive, but <0.25 for Gram-negative pathogens with MIC ≥0.25 mg/L. With the exception of the first 24 hours of therapy, obesity affected PTA only marginally. Pharmacokinetic parameters in DFI patients were similar to those reported for healthy volunteers, indicating the appropriateness of the standard dose of moxifloxacin. Overall clinical efficacy has been shown previously, but PTA is limited in a subpopulation infected with formally susceptible Gram-negative pathogens close to the EUCAST breakpoint.
authors.affiliation: Department of Clinical Pharmacy and﻿ Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.
authors.forename: Sebastian G
authors.initials: SG
authors.lastname: Wicha
authors.forename: Thomas
authors.initials: T
authors.lastname: Haak
authors.forename: Karl
authors.initials: K
authors.lastname: Zink
authors.forename: Frieder
authors.initials: F
authors.lastname: Kees
authors.forename: Charlotte
authors.initials: C
authors.lastname: Kloft
authors.forename: Martin G
authors.initials: MG
authors.lastname: Kees
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D003920:Diabetes Mellitus / Q000382:microbiology*; D017719:Diabetic Foot / Q000188:drug therapy* / Q000382:microbiology*; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000472:pathogenicity; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009010:Monte Carlo Method; D000077266:Moxifloxacin
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin
keywords: complicated skin and skin structure infections; fluoroquinolones; pharmacokinetic/pharmacodynamic analysis; tissue concentrations