Assessment of optimal initial dosing regimen with vancomycin pharmacokinetics model in very low birth weight neonates

Pharmacokinetic of vancomycin in very low birth weight neonates showed big variety, and limited data were available due to very minor population. These facts make it difficult to adjust its optimal initial dosage. Therefore, this study was to develop optimal dosing regimen of vancomycin in very low birth weight neonates.

Between 2010 and 2015, low birth weight neonates (≤1500 g) were included in a population pharmacokinetics analysis. Based on the pharmacokinetic parameters we estimated, we simulated individual blood concentrations of vancomycin and evaluated the probability of its pharmacokinetics/pharmacodynamics (PK/PD) target attainment, such as 24-h area under the concentration-time curve (AUC₂₄)/MIC (≥400) and blood trough concentration (10-20 μg/mL), as primary measure for several dosing regimens by Monte Carlo simulation method.

Ten patients were prescribed vancomycin and detected its blood concentrations as routine pharmacy practice to adjust the dosage. A one-compartment model was used and clearance significantly correlated with serum creatinine and the volume of infusion. In this model, vancomycin dose at 10 mg/kg three times a day (TID) was predicted to result 86.7% of neonates for an MIC of 1 μg/mL achieving AUC/MIC of ≥400 and 30.6% of the neonates for an MIC of 2 μg/mL. Moreover, the probability of reaching the target trough concentration was 70.5% for patients treated with vancomycin 10 mg/kg TID.

We recommended vancomycin 10 mg/kg TID as initial dosage regimens for low birth weight neonates infected with the pathogens showed MIC of ≤1 μg/mL.