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

Evelyne Jacqz-Aigrain, Stéphanie Leroux, Alison H. Thomson, Karel Allegaert, Edmund V. Capparelli, Valérie 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

Research output: Contribution to journalArticle

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 (US)
Pages (from-to)2128-2138
Number of pages11
JournalThe Journal of antimicrobial chemotherapy
Volume74
Issue number8
DOIs
StatePublished - Aug 1 2019

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Vancomycin
Meta-Analysis
Pharmacokinetics
Newborn Infant
Population
Creatinine
Weights and Measures
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

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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. / 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.

In: The Journal of antimicrobial chemotherapy, Vol. 74, No. 8, 01.08.2019, p. 2128-2138.

Research output: Contribution to journalArticle

Jacqz-Aigrain, E, Leroux, S, Thomson, AH, Allegaert, K, Capparelli, EV, Biran, V, Simon, N, Meibohm, B, Lo, YL, Marques, R, Peris, JE, Lutsar, I, Saito, J, Nakamura, H, van den Anker, JN, 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', The Journal of antimicrobial chemotherapy, vol. 74, no. 8, pp. 2128-2138. https://doi.org/10.1093/jac/dkz158
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. / Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants. In: The Journal of antimicrobial chemotherapy. 2019 ; Vol. 74, No. 8. pp. 2128-2138.
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AU - Allegaert, Karel

AU - Capparelli, Edmund V.

AU - Biran, Valérie

AU - Simon, Nicolas

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AU - Lo, Yoke Lin

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AU - Peris, José Esteban

AU - Lutsar, Irja

AU - Saito, Jumpei

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AU - Zhao, Wei

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N2 - 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.

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