A priori optimization of levofloxacin dose regimen based on a population pharmacokinetics model

Abstract

Background: Levofloxacin is a broad-spectrum fluoroquinolone with pharmacokinetic characteristics that facilitate its use in many types of infections.

Objectives: To develop a population pharmacokinetics (PK) model of levofloxacin and to identify covariates influencing its PK, to determine the best dose regimens for pharmacodynamic target achievement.

Patients and methods: Patients treated with levofloxacin were retrospectively included from December 2014 to February 2021. The population PK analysis was performed using Pmetrics. Multiple covariates were tested: age, height, weight, ideal weight, BMI, body surface area (BSA), plasma protein and creatinine levels, and absolute glomerular filtration rate (aGFR) calculated from the chronic kidney disease-epidemiology formula and BSA. Dosing simulations were performed for all combinations of covariates and MIC values. The AUC0-24/MIC ratio targets were 50 for Streptococcus pneumoniae and 125 for other bacterial species.

Results: A total of 39 patients were included, of which 23 patients were hospitalized in ICUs. The population PK analysis was performed on 175 plasma concentrations of levofloxacin. A two-compartment model best described levofloxacin PK with three covariates: aGFR for the elimination rate constant and both plasma protein level and BSA for the central compartment volume. Tables with proposed dose regimens according to patient covariates and pharmacodynamic targets values are provided.

Conclusions: This study provided a priori dose regimen adaptation based on a population PK model for levofloxacin. For patients with increased renal function or infection by high MIC bacteria, the pharmacodynamic target could not be reliably achieved with standard dosages.