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

Author:

He Yun‐Ying1,Sun Jing12,Wu Yue‐E1,Wang Yong‐Bin3,van den Anker John456,Hao Guo‐Xiang1,Sun De‐Qing2,Zhao Wei127ORCID

Affiliation:

1. Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine Shandong University Jinan China

2. Department of Pharmacy The Second Hospital of Shandong University Jinan China

3. Department of Respiratory The Second Hospital of Shandong University Jinan China

4. Division of Clinical Pharmacology, Children's National Hospital Washington District of Columbia USA

5. Departments of Pediatrics, Pharmacology & Physiology, Genomics and Precision Medicine, School of Medicine and Health Sciences George Washington University Washington District of Columbia USA

6. Department of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel University of Basel Basel Switzerland

7. Department of Clinical Pharmacy, Clinical Trial Center, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital Shandong Engineering and Technology Research Center for Pediatric Drug Development, Medicine and Health Key Laboratory of Clinical Pharmacy Jinan Shandong China

Abstract

AimsLevofloxacin 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.MethodsThis 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.ResultsData 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.ConclusionsThe population pharmacokinetic model of levofloxacin in elderly patients with pneumonia was established, and the dose optimization of levofloxacin was completed through Monte Carlo simulation.

Funder

National Key Research and Development Program of China

Publisher

Wiley

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