Establishment of a population pharmacokinetic model for linezolid in neonates with sepsis
10.7499/j.issn.1008-8830.2406078
- VernacularTitle:利奈唑胺在败血症新生儿中的群体药动学模型构建
- Author:
Zong-Tai FENG
1
;
Lian TANG
;
Zu-Ming YANG
;
Chu-Chu GAO
;
Jia-Hui LI
;
Yan CAI
;
Lu-Fen DUAN
Author Information
1. 苏州市立医院/南京医科大学附属苏州医院/南京医科大学姑苏学院新生儿科,江苏苏州 215002
- Keywords:
Sepsis;
Linezolid;
Population pharmacokinetics;
Therapeutic drug monitoring;
Monte Carlo simulation;
Neonate
- From:
Chinese Journal of Contemporary Pediatrics
2024;26(11):1162-1168
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.
