Optimizing Linezolid Dosing by Renal Function: A Population Pharmacokinetic Study

Objectives Linezolid is administered at a fixed dose of 600 mg twice daily for the treatment of Gram‐positive infections. However, recent population pharmacokinetic studies reveal considerable interpatient variability, resulting in subtherapeutic or supratherapeutic drug exposures. This study aimed to describe the pharmacokinetics of linezolid in hospitalized infectious patients across varying degrees of renal function and propose optimized dosing strategies. Methods Population pharmacokinetic modeling was performed using Monolix Version 2024R1. The model was evaluated using goodness‐of‐fit plots, bootstrap analysis, and prediction‐corrected visual predictive checks. Appropriate dosing regimens for different levels of renal function and minimum inhibitory concentrations were proposed by Monte Carlo simulations. Results Fifty‐five adult patients with a total of 178 linezolid concentration measurements were included. A two‐compartment model with first‐order absorption and linear elimination best described the pharmacokinetic data. Volume of distribution and clearances were scaled using an allometric weight model. In addition, creatinine clearance (CLcr) significantly affected linezolid clearance. Simulation results suggested that patients with CLcr ≤ 30 mL/min may require reduced doses (600–900 mg daily), whereas those with CLcr ≥ 110 mL/min may benefit from increased doses (600 mg every 8 h). Conclusions Individualization of linezolid dosing based on renal function is warranted. Therapeutic drug monitoring is recommended for patients with impaired or augmented renal clearance to optimize the therapeutic efficacy and minimize the risk of toxicity.