DDMODEL00000034: PK of moxifloxacin in patients with diabetic foot infections

  public model
Short description:
Population PK model of moxifloxacin in patients with diabetic foot infections
Original code
  • Population pharmacokinetics and target attainment analysis of moxifloxacin in patients with diabetic foot infections.
  • Wicha SG, Haak T, Zink K, Kees F, Kloft C, Kees MG
  • Journal of clinical pharmacology, 6/2015, Volume 55, Issue 6, pages: 639-646
  • Department of Clinical Pharmacy and? Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany.
  • 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.
Sebastian Wicha, Gunnar Yngman
Context of model development: Variability sources in PK and PD (CYP, Renal, Biomarkers); Therapeutic Drug Monitoring; Patient Population Selection and Bridging between Population (Pediatrics, Elderly, Obese);
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: Moxifloxacin population PK in patients with diabetic foot infections, probability of PK/PD target attainment analysis, exploration of covariates weight and renal function on PK/PD;
Modelling task in scope: estimation; simulation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Anti-infectives;
Annotations are correct.
This model is not certified.
  • Model owner: Sebastian Wicha
  • Submitted: Dec 11, 2015 9:16:38 AM
  • Last Modified: May 18, 2016 4:46:28 PM
Revisions
  • Version: 14 public model Download this version
    • Submitted on: May 18, 2016 4:46:28 PM
    • Submitted by: Sebastian Wicha
    • With comment: Updated model annotations.
  • Version: 10 public model Download this version
    • Submitted on: Dec 11, 2015 9:16:38 AM
    • Submitted by: Sebastian Wicha
    • With comment: Edited model metadata online.
 
Help