title: Moxifloxacin dosing in post-bariatric surgery patients.
abstract: BACKGROUND
  Given the ever increasing number of obese patients and obesity related bypass surgery, dosing recommendations in the post-bypass population are needed. Using a population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) simulations, we investigated whether adequate moxifloxacin concentrations are achieved in this population.
  
  
  METHODS
  In this modelling and simulation study we used data from a trial on moxifloxacin PK. In this trial, volunteers who had previously undergone bariatric surgery (at least 6 months prior to inclusion), received two doses (intravenous and oral) of 400 mg moxifloxacin administered on two occasions.
  
  
  RESULTS
  In contrast to other papers, we found that moxifloxacin PK were best described by a three compartmental model using lean body mass (LBM) as a predictor for moxifloxacin clearance. Furthermore, we showed that the probability of target attainment for bacterial eradication against a hypothetical Streptococcus pneumoniae infection is compromised in patients with higher LBM, especially when targeting microorganisms with minimum inhibitory concentrations (MICs) of 0.5 mg l(-1) or higher (probability of target attainment (PTA) approaching zero). When considering the targets for suppression of bacterial resistance formation, even at MIC values as low as 0.25 mg l(-1) , standard moxifloxacin dosing does not attain adequate levels in this population. Furthermore, for patients with a LBM of 78 kg or higher, the probability of hitting this target approaches zero.
  
  
  CONCLUSIONS
  Throughout our PK-PD simulation study, it became apparent that, whenever optimal bacterial resistance suppression is deemed necessary, the standard moxifloxacin dosing will not be sufficient. Furthermore, our study emphasizes the need for a LBM based individualized dosing of moxifloxacin in this patient population.
authors: Laboratory of Medical Biochemistry and Clinical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors: Pieter
authors: P
authors: Colin
authors: Douglas J
authors: DJ
authors: Eleveld
authors: Michel M R F
authors: MM
authors: Struys
authors: Huybrecht
authors: H
authors: T'Jollyn
authors: Luc M Van
authors: LM
authors: Bortel
authors: Johannes
authors: J
authors: Ruige
authors: Jan
authors: J
authors: De Waele
authors: Jan
authors: J
authors: Van Bocxlaer
authors: Koen
authors: K
authors: Boussery
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D050110:Bariatric Surgery; D003198:Computer Simulation; D054796:Drug Dosage Calculations; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000077266:Moxifloxacin; D009765:Obesity / Q000601:surgery*; D011182:Postoperative Care
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D000077266:Moxifloxacin
keywords: NONMEM; PK-PD; bariatric surgery; moxifloxacin; pharmacokinetics