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Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study

Florian Lemaitre1, Fabien Fily2, Jean-Baptiste Foulquier1

  • 1Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France; INSERM, Centre d'Investigation Clinique, CIC 1414, F-35000 Rennes, France.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|August 26, 2021
PubMed

Insights

Optimizing fluoroquinolone treatment for osteoarticular infections (OAI) requires accurate drug exposure monitoring. A new limited sampling strategy (LSS) using three blood samples effectively estimates ofloxacin and levofloxacin AUC, enabling precise dosing for OAI patients.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Clinical Pharmacy

Background:

  • Fluoroquinolone efficacy in osteoarticular infections (OAI) correlates with AUC/MIC ratio, but clinical data and practical AUC estimation methods are limited.
  • Staphylococcus species, a common cause of OAI, require specific therapeutic drug monitoring for optimal fluoroquinolone treatment.
  • Existing methods for determining drug exposure (AUC) in OAI patients are complex and not readily available in clinical settings.

Purpose of the Study:

  • To develop and validate a pharmacokinetic model for ofloxacin in OAI patients.
  • To establish a simple and effective limited sampling strategy (LSS) for estimating ofloxacin and levofloxacin exposure.
  • To determine optimal dosing regimens for fluoroquinolones in OAI using probability of target attainment (PTA) simulations.

Main Methods:

  • Prospective, single-center study involving 30 OAI patients treated with ofloxacin.
  • Pharmacokinetic modeling using Monolix software, with external validation using levofloxacin data.
  • Monte Carlo simulations to assess probability of target attainment (PTA) for various dosing regimens.
  • Development and evaluation of a limited sampling strategy (LSS) based on drug concentration measurements.

Main Results:

  • Ofloxacin pharmacokinetics was best described by a bicompartmental model with first-order elimination and transit compartment absorption.
  • Renal function (CKD-EPI) and sex were significant covariates, explaining substantial variability in ofloxacin pharmacokinetics.
  • A 3-sample LSS (pre-dose, 1h, 3h) demonstrated high accuracy (R² adjusted >90%) for estimating AUC for both twice and thrice daily dosing regimens.

Conclusions:

  • A practical 3-sample limited sampling strategy (LSS) accurately estimates ofloxacin and levofloxacin AUC in OAI patients.
  • This LSS facilitates optimized drug dosing, enhancing the efficacy of fluoroquinolone treatment for osteoarticular infections.
  • The findings support improved therapeutic drug monitoring for fluoroquinolones in managing OAI.
Keywords:
Bone infectionJoint infectionModelingOfloxacinPharmacokinetics

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