Population Pharmacokinetic Analysis and Dose Regimen Optimization in Japanese Infants with an Extremely Low Birth Weight

摘要

Vancomycin is a synthetic antibiotic effective against Gram-positive pathogens. Although the clinical applicability of vancomycin for infants has been increasing, the pharmacokinetic data for vancomycin in extremely low-birth-weight infants are limited. The aim of this study was to construct a population pharmacokinetics model for vancomycin in extremely-low-birth-weight infants and establish an optimal dosage regimen. We enrolled children aged less than 1 year with a birth weight of less than 1,000 g and body weight at vancomycin prescription of less than 1,500 g. Pharmacokinetic data from 19 patients were analyzed, and a population pharmacokinetics model was developed using nonlinear mixed-effects modeling software. Goodness-of-fit plots, a nonparametric bootstrap analysis, and a prediction-corrected visual predictive check were employed to evaluate the final model. The dosage regimen was optimized based on the final model. The pharmacokinetic data fit a one-compartment model with first-order elimination, and body weight and estimated serum creatinine level were used as significant covariates. In a simulation using the final model, the optimal dosage regimen, especially when the serum creatinine level (>0.6 mg/dl) was high, was 5.0 to 7.5 mg/kg of body weight twice a day every 12 h; this was required to reduce the dosage compared with that in previous studies. The recommended doses based on the current target time course concentration curves may not be appropriate for extremely-low-birth-weight infants.