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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2019
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my.um.eprints.240982020-03-23T07:38:10Z http://eprints.um.edu.my/24098/ 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 R Medicine 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. Oxford University Press 2019 Article PeerReviewed Jacqz-Aigrain, Evelyne and Leroux, Stéphanie and Thomson, Alison H. and Allegaert, Karel and Capparelli, Edmund V. and Biran, Valérie and Simon, Nicolas and Meibohm, Bernd and Lo, Yoke Lin and Marques, Remedios and Peris, José-Esteban and Lutsar, Irja and Saito, Jumpei and Nakamura, Hidefumi and van den Anker, Johannes N. and Sharland, Mike and Zhao, Wei (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). pp. 2128-2138. ISSN 0305-7453 https://doi.org/10.1093/jac/dkz158 doi:10.1093/jac/dkz158 |
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R Medicine 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 |
| description |
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. |
| format |
Article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Jacqz-Aigrain, Evelyne |
| title |
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants |
| title_short |
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants |
| title_full |
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants |
| title_fullStr |
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants |
| title_full_unstemmed |
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants |
| title_sort |
population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants |
| publisher |
Oxford University Press |
| publishDate |
2019 |
| url |
http://eprints.um.edu.my/24098/ https://doi.org/10.1093/jac/dkz158 |
| _version_ |
1662755222726901760 |
| score |
13.211869 |