Population pharmacokinetics and dose optimization of levofloxacin in elderly patients with pneumonia

Br J Clin Pharmacol. 2024 May;90(5):1213-1221. doi: 10.1111/bcp.16003. Epub 2024 Feb 5.

Abstract

Aims: Levofloxacin is a quinolone antibiotic with a broad antibacterial spectrum. It is frequently used in elderly patients with pneumonia. The pharmacokinetic profile of elderly patients changes with age, but data on the pharmacokinetics of levofloxacin in these patients are limited. The aim of this study was to establish a population pharmacokinetic model of levofloxacin in elderly patients with pneumonia and to optimize individualized dosing regimens based on this newly developed model.

Methods: This is a prospective, open-label pharmacokinetic study in elderly patients with pneumonia. Blood samples were collected using an opportunistic approach. The plasma concentrations of levofloxacin were determined by high-performance liquid chromatography. A population pharmacokinetic model was established using nonlinear mixed-effect model software. Monte Carlo simulations were used for dose simulation and dose optimization.

Results: Data from 51 elderly patients with pneumonia were used for the population pharmacokinetic analysis. A one-compartment model with first-order elimination was most suitable for describing the data, and the estimated glomerular filtration rate was the only covariate that had a significant impact on the model. The final model estimated that the mean clearance of levofloxacin in elderly patients with pneumonia was 5.26 L/h. Monte Carlo simulation results showed that the optimal dosing regimen for levofloxacin was 750 mg once a day in elderly patients with pneumonia, with a minimum inhibitory concentration of 2 mg/L.

Conclusions: The population pharmacokinetic model of levofloxacin in elderly patients with pneumonia was established, and the dose optimization of levofloxacin was completed through Monte Carlo simulation.

Keywords: dosing optimization; elderly; levofloxacin; population pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents* / administration & dosage
  • Anti-Bacterial Agents* / pharmacokinetics
  • Computer Simulation
  • Dose-Response Relationship, Drug
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Levofloxacin* / administration & dosage
  • Levofloxacin* / blood
  • Levofloxacin* / pharmacokinetics
  • Male
  • Models, Biological*
  • Monte Carlo Method*
  • Pneumonia* / drug therapy
  • Prospective Studies

Substances

  • Levofloxacin
  • Anti-Bacterial Agents