Population Pharmacokinetics and Dosage Optimization of Linezolid in Chinese Older Patients

Purpose The objective of this study was to assessed the pharmacokinetics and pharmacodynamics of linezolid in a retrospective cohort of hospitalized Chinese older patients. Methods Patients >60 years of age, who received intravenous linezolid 600 mg, were included. A population pharmacokinetics (PPK) model was established using nonlinear mixed-effects modeling. The predictive performance of the final model was assessed using goodness-of-fit plots, bootstrap analyses, and visual predictive checks. Monte Carlo simulations were used to evaluate the achievement of a pharmacodynamics target for the area under the serum concentration–time curve/minimum inhibitory concentration (AUC 0–24 /MIC). Results A total of 210 samples were collected from 120 older patients. A one-compartment PPK model with linear elimination was found to best predict the linezolid plasma concentrations. Linezolid clearance (CL) was 4.22 L h -1 and the volume of distribution (V d ) was 45.80 L along with serum uric acid (SUA) as a significant covariate of CL. Conclusion Based on the study results, we concluded that the standard dose was associated with a risk of overexposure in older patients, particularly those with high SUA values; these patients would benefit from a lower dose (300 mg every 12 h). This study would help in the therapeutic drug monitoring of linezolid in older patients in the future.