Development of an Adjustment Assistance Tool Dosage of Fluoroquinolones in a Population Pharmacokinetic Model
Status:
Completed
Trial end date:
2016-12-01
Target enrollment:
Participant gender:
Summary
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.