A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C.

BACKGROUND AND OBJECTIVES

Renal function has an important influence on the pharmacokinetics of vancomycin, and serum cystatin C (CysC) exhibits accurate predictive performance as a marker for renal function. This study aimed to develop a population pharmacokinetics (PopPK) model of vancomycin based on serum CysC in pediatric patients. In addition, vancomycin dosage was optimized with the area under the serum concentration-time curve over 24 h (AUC)/minimum inhibitory concentration (MIC) ratio in the target range of 400-700 and the steady-state trough concentration (C).

METHODS

Data were retrospectively obtained from pediatric patients aged 2-18 years who received vancomycin treatment for infection from January 2014 to June 2019. PopPK analysis and Monte Carlo simulations were conducted using nonlinear mixed effects model (NONMEM) software.

RESULTS

A total of 220 children were included. Serum CysC and age were significant covariates affecting the pharmacokinetics of vancomycin. The final typical value of clearance was 2.25 L/h; the volume of distribution was 8.17 L. The average probability of target attainment values of AUC/MIC ratios within 400-700 in the 2-7, 7-12, and 12-18 years age groups were 66.1%, 68.1% and 66.5%, respectively. The median C values of vancomycin for the 2-7, 7-12, and 12-18 years age groups were 7.49-11.84, 5.98-11.32, and 5.15-11.39 mg/L, respectively, and were highly correlated with AUC/MIC ratios in the range of 400-700 when the MIC was 1 mg/L.

CONCLUSIONS

The pharmacokinetic parameters for vancomycin in pediatric patients were estimated using a serum CysC model. The simulated dosages provide a reference for vancomycin therapy.