Development of an Adjustment Assistance Tool Dosage of Fluoroquinolones in a Population Pharmacokinetic Model
Development of an Adjustment Assistance Tool Dosage of Fluoroquinolones in a Population Pharmacokinetic Model
Fluoroquinolones (FQ) are among pivotal antibiotic treatments in difficult-to-treat
 infections. Their efficacy has been shown to be linked to the ratio area under the curve
 (AUC) of their plasma concentrations over the minimum inhibitory concentration (MIC) of the
 bacteria treated. Eventually, Forrest et al., reported in gram-negative infections that an
 AUC/MIC above 125 conducted to a 80 to 90% clinical success whereas success decrease to 30 to
 40% in patients with an AUC/MIC below this threshold. These results have been reproduced
 recently by Zelenitsky et al. in intensive care unit (ICU) patients with threshold similar to
 the one obtained by Forrest et al. Lastly, elevated concentrations of FQ should be related
 with the onset of adverse events. Thus, therapeutic drug monitoring (TDM) of FQ appears of
 potential interest, particularly in case of severe infections (intensive care unit (ICU)
 patients) or complicated and cost-related infections (osteoarticular infected (OAI)
 patients), with an increasing level of evidence of its use.

 However, FQ TDM requires access to the full AUC of the drug with the need of many samples
 drawn to patients. This appears to be irreconcilable with clinical practice but can be
 achieved using population pharmacokinetic (PkPop) modelling. PkPop allows estimating
 pharmacokinetic parameters of the drug by introducing covariates (demographic, biological,
 clinical…) and modelling inter-individual pharmacokinetic variability. The model created
 allows then accessing to individual parameters of patients and thus, estimating
 concentrations and AUC of the FQ. This approach may also be used in clinical practice to
 determine a limited sampling strategy allowing an adequate estimation of AUC with a minimum
 of samples.
Open, prospective, monocentric pharmacokinetic study
Inclusion Criteria:

 -  Age over 18 years

 -  Patients in intensive care : Infection treated with ciprofloxacin IV

 -  Osteoarticular infected patients : infection treated with oral ofloxacin

 -  Written consent to participate in the study

 Exclusion Criteria:

 -  Pregnancy

 -  Adults subject to legal protection or deprived of their liberty