RESUMEN
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.
Asunto(s)
Antibacterianos , Levofloxacino , Modelos Biológicos , Método de Montecarlo , Neumonía , Humanos , Levofloxacino/farmacocinética , Levofloxacino/administración & dosificación , Levofloxacino/sangre , Anciano , Masculino , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Femenino , Anciano de 80 o más Años , Estudios Prospectivos , Neumonía/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Tasa de Filtración Glomerular , Simulación por ComputadorRESUMEN
INTRODUCTION: ß-Lactams are the most widely used antibiotics in children. Their optimal dosing is essential to maximize their efficacy, while minimizing the risk for toxicity and the further emergence of antimicrobial resistance. However, most ß-lactams were developed and licensed long before regulatory changes mandated pharmacokinetic studies in children. As a result, pediatric dosing practices are poorly harmonized and off-label use remains common today. AREAS COVERED: ß-Lactam pharmacokinetics and dose optimization strategies in pediatrics, including fixed dose regimens, therapeutic drug monitoring, and model-informed precision dosing are reviewed. EXPERT OPINION/COMMENTARY: Standard pediatric doses can result in subtherapeutic exposure and non-target attainment for specific patient subpopulations (neonates, critically ill children, e.g.). Such patients could benefit greatly from more individualized approaches to dose optimization, beyond a relatively simple dose adaptation based on weight, age, or renal function. In this context, Therapeutic Drug Monitoring (TDM) and Model-Informed Precision Dosing (MIPD) emerge as particularly promising avenues. Obstacles to their implementation include the lack of strong evidence of clinical benefit due to the paucity of randomized clinical trials, of standardized assays for monitoring concentrations, or of adequate markers for renal function. The development of precision medicine tools is urgently needed to individualize therapy in vulnerable pediatric subpopulations.