Dose optimization of vancomycin in critically ill pediatric patients: A population pharmacokinetic study

Vancomycin has been the first-line therapy for treatment of severe Gram-positive infections in critically ill pediatric patients; however, high inter- and intra-individual variability on pharmacokinetics posed significant challenges in selecting the optimal dose. This study aimed to develop a population pharmacokinetic (popPK) model for vancomycin in critically ill pediatric patients and optimize the initial dose based on this model. Therapeutics drug monitoring (TDM) data was collected retrospectively from 245 patients receiving intravenous vancomycin at the Pediatric Intensive Care Unit (PICU), Vietnam National Children’s Hospital. Population pharmacokinetics modeling and Monte Carlo simulation were performed with the AUC target of 400–800 mg×h/L to optimize efficacy and minimize toxicity with the help of NONMEM®7.5.1. The results showed that a two-compartment model, allometric scaling by weight with first-order elimination and combined additive and proportional error best fitted data. Typical values of central and peripheral volumes of distribution were 0.180 and 0.297 L/kg, respectively. Typical clearance of 0.260 was predicted by body weight, serum creatinine (SCr), and postmenstrual age. The optimal doses adjusted by age and SCr to achieve PTA range from 25–60 mg/kg per day for infants < 3 months, 30–75 mg/kg per day for 3 months to 1 year, and 40–80 mg/kg per day for children ≥ 1 year with SCr of >80, 40–80, 20–40, and <20 µmol/L were identified, respectively. In conclusion, a popPK model of vancomycin in PICU was successfully developed, and the initial dosing regimen was optimized. TDM with the integration of the popPK model into the Bayesian program following external validation is suggested.