Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Biomedicine and Pharmacotherapy Année : 2021

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

Résumé

Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R(2) adjusted = 91.1% and 95.0%, outliers = 4.8% and 5.0%, respectively). PTA allows choosing the best drug and dosage according to various hypotheses. A simple 3-sample protocol (pre-dose, 1 h after intake and 3 h after intake) to estimate ofloxacin and levofloxacin AUC allows optimal drug dosage for the treatment of osteoarticular infections.
Fichier principal
Vignette du fichier
1-s2.0-S0753332221008362-main.pdf (2.07 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03333579 , version 1 (03-09-2021)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Florian Lemaitre, Fabien Fily, Jean-Baptiste Foulquier, Matthieu Revest, Vincent Jullien, et al.. Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study. Biomedicine and Pharmacotherapy, 2021, 142, pp.112053. ⟨10.1016/j.biopha.2021.112053⟩. ⟨hal-03333579⟩
143 Consultations
60 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More