Establishment of a population pharmacokinetics model of vancomycin in 94 infants with septicemia and its application in individualized therapy

Abstract

Background

We aim to develop a population pharmacokinetics (PopPK) model of vancomycin for the treatment of septicemia in infants younger than one year. Factors influence of the PK was investigated to optimize vancomycin dosing regimen.

Methods

The nonlinear mixed effects modelling software (NONMEM) was used to develop the PopPK model of vancomycin. The stability and predictive ability of the final model were assessed by using normalized prediction distribution errors (NPDE) and bootstrap methods. The final model was subjected to Monte Carlo simulation in order to determine the optimal dose.

Results

A total of 205 trough and peak concentrations in 94 infants (0–1 year of age) with septicemia were analyzed. The interindividual variability of the PK parameter was described by the exponential model. Residual error was better described by the proportional model than the mixed proportional and addition models. Serum creatinine concentration and body weight are the major factors that affect the PK parameters of vancomycin. The clearance was shown to be higher when ceftriaxone was co-treated. More than two model evaluation methods showed better stability than the base model, with superior predictive performance, which can develop individualized dosing regimens for clinical reference. Through prediction of final model, the trough concentration was more likely < 5 mg/L when a routine dose of 10 mg/kg is administered every 6 h to 3–9-month-old infants. Therefore, the dose should be increased in the treatment of infant septicemia.

Conclusions

The stable and effective PopPK model of vancomycin in Chinese infants with septicemia was established. This model has satisfactory predictive ability for clinically individualized dosing regimens in this vulnerable population.