External Validation of a Vancomycin Population Pharmacokinetic Model and Developing a New Dosage Regimen in Neonates

Background and Objective Vancomycin is the drug of choice in the treatment of MRSA infections. In a published vancomycin population pharmacokinetic study on neonates in Singapore healthcare institutions, it was found that vancomycin clearance was predicted by weight, postmenstrual age, and serum creatinine. The aim of this study was to externally validate the vancomycin population pharmacokinetic model to develop a new dosage regimen in neonates, and to compare this regimen with the existing institutional and NeoFax (R) dosage regimens. Methods A retrospective chart review of neonates who received vancomycin therapy and therapeutic drug monitoring was conducted. The median prediction error percentage was calculated to assess bias, while the median absolute prediction error percentage and the root mean squared error percentage were calculated to assess precision. The new dosage regimen was developed using Monte Carlo simulation. Results A total of 20 neonates were included in the external validation dataset. Eighteen of them were premature, with a median gestational age of 27.7 (25.9-31.5) weeks and postmenstrual age of 30.5 (27.3-34.3) weeks at the point of vancomycin initiation. No apparent systematic bias was found in the predictions of the model. The external validation performed in the current study found the model to be generally unbiased. Our new vancomycin dosage regimen was able to achieve target trough concentrations and area under the curve (AUC(24)) at a greater proportion as compared to existing institutional and NeoFax (R) dosage regimens. Conclusion The pharmacokinetic model built in the previous study can be used to conduct reliable population simulations of our Asian neonatal population in Singapore. The new dosage regimen was able to achieve target trough concentrations and AUC(24) better than existing institutional and NeoFax (R) dosage regimens.