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

Evelyne Jacqz-Aigrain, Stephanie Leroux, Alison H. Thomson, Karel Allegaert, Edmund V. Capparelli, Valerie Biran, Nicolas Simon, Bernd Meibohm, Yoke-Lin Lo, Remedios Marques, José-Esteban Peris, Irja Lutsar, Jumpei Saito , Hidefumi Nakamura , Johannes N. van den Anker, Mike Sharland, Wei Zhao

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Abstract

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.

Original languageEnglish
Pages (from-to)2128-2138
Number of pages11
JournalJournal of Antimicrobial Chemotherapy
Volume74
Issue number8
Early online date2 May 2019
DOIs
Publication statusPublished - 31 Aug 2019

Keywords

  • vancomycin
  • steady state
  • drug loading dose
  • drug maintenance dose
  • creatinine tests
  • infusion procedures

Cite this

Jacqz-Aigrain, E., Leroux, S., Thomson, A. H., Allegaert, K., Capparelli, E. V., Biran, V., Simon, N., Meibohm, B., Lo, Y-L., Marques, R., Peris, J-E., Lutsar, I., Saito , J., Nakamura , H., van den Anker, J. N., Sharland, M., & Zhao, W. (2019). Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants. Journal of Antimicrobial Chemotherapy, 74(8), 2128-2138. https://doi.org/10.1093/jac/dkz158