Population pharmacokinetics and dosing optimization of linezolid in pediatric patients [Clinical Therapeutics]

Background: Linezolid is a synthetic antibiotic very effective in the treatment of infections caused by Gram-positive pathogens. Although the clinical application of linezolid in children increased progressively, data on linezolid pharmacokinetics in pediatric patients are very limited. The aim of this study was to develop a population pharmacokinetic model for linezolid in children and optimize dosing strategy in order to improve therapeutic efficacy.

Methods: We performed a prospective pharmacokinetic study of pediatric patients aged 0-12 years. The population pharmacokinetic model was developed using NONMEM program. Goodness-of-fit plots, nonparametric bootstrap, normalized prediction distribution errors and visual predictive check were employed to evaluate the final model. The dosing regimen was optimized based on the final model.

Results: The pharmacokinetic data from 112 pediatric patients aged from 0.03 to 11.9 years were analysed. The pharmacokinetics could be best described by a one compartment model with first order elimination along with body weight and estimated glomerular filtration rate as significant covariates. Simulations demonstrated that the currently approved dosage of 10 mg/kg q8h would lead to a high risk of underdosing for children in the presence of bacteria with MIC of ≥ 2 mg/L. To reach the pharmacokinetic target, an elevated dosage of 15 or 20 mg/kg q8h may be required for them.

Conclusion: The population pharmacokinetics of linezolid were characterized in pediatric patients, and simulations provide an evidence-based approach for linezolid dosage individualization.

http://bit.ly/2FqE5zf