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Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants

OBJECTIVES: In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. METHODS: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to desi...

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Main Authors: Jacqz-Aigrain, Evelyne, Leroux, Stéphanie, Thomson, Alison H., Allegaert, Karel, Capparelli, Edmund V., Biran, Valérie, Simon, Nicolas, Meibohm, Bernd, Lo, Yoke Lin, Marques, Remedios, Peris, José-Esteban, Lutsar, Irja, Saito, Jumpei, Nakamura, Hidefumi, van den Anker, Johannes N., Sharland, Mike, Zhao, Wei
Format: Article
Published: Oxford University Press 2019
Subjects:
R Medicine
Online Access:http://eprints.um.edu.my/24098/
https://doi.org/10.1093/jac/dkz158
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Summary:OBJECTIVES: In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. METHODS: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates. RESULTS: A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0-24 target earlier than a standard 'Blue Book' dosage regimen in >89% of the treated patients. CONCLUSIONS: The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc. © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.

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