Clinical Microbiology and Antimicrobial Chemotherapy. 2026; 28(1):72-80
To study pharmacokinetics (PK) and develop a pharmacokinetic/pharmacodynamic (PK/PD) model of linezolid for preterm infants, based on therapeutic drug monitoring (TDM) data.
The PK/PD analysis included data from therapeutic drug monitoring (TDM) of 24 premature infants, taking into account the repeated TDM procedure – a total of 27 occasions and 54 measurements of linezolid concentration. Quantitative determination of linezolid concentrations in the blood plasma of patients was carried out using the analytical method of measurement by HPLC-UV previously developed on the basis of the educational and scientific laboratory for the study of drug safety at the Department of General and Clinical Pharmacology of the RUDN University in the City Clinical Hospital No. 24.
Total clearance and volume of distribution values of linezolid in premature newborns estimated in the study were consistent with those previously reported in the literature. A significant interindividual PK variability was observed (coefficient of variation – 42-89%), resulting in poor predictability of the Сtrough and Cmax levels at the end of infusion when the standard dosing regimen of linezolid 10 mg/kg thrice daily was used. Such pronounced interindividual variability of PK parameters, combined with a relatively limited sample size, precluded probably development from the available TDM data of a multivariate regression model that could predict the individual PK parameter values for the majority of the included premature infants based on their covariates with acceptable accuracy.
The observed discrepancies in the dosage regimens, which are considered optimal in different published PK/PD studies for premature newborns, indicate in favor of using standard regimens only to individualize the initial dosing based on patient covariates. Further dosage adjustments should preferably be made based on the patient’s TDM data. Specialized software for Bayesian population modeling approach will allow to personalize linezolid therapy based on rare TDM measurements without waiting for the steady state, which is especially important for the premature infant population.