Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants
- Jacqz-Aigrain, Evelyne ORCID University Paris Diderot, Sorbonne Paris Cité, Paris, France
- Leroux, Stéphanie Division of Neonatology, Department of Child and Adolescent Medicine, CHU de Rennes, Rennes, France
- Thomson, Alison H Pharmacy Department, Glasgow Royal Infirmary, Glasgow, UK
- Allegaert, Karel Intensive Care, Erasmus MC – Sophia Children's Hospital, Rotterdam, The Netherlands
- Capparelli, Edmund V Pediatric Pharmacology and Drug Discovery, University of California, San Diego, CA, USA
- Biran, Valérie Neonatal Intensive Care Unit, Hôpital Robert Debré, Paris, France
- Simon, Nicolas Aix Marseille University, INSERM, IRD, SESSTIM, Marseille, France
- Meibohm, Bernd Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN, USA
- Lo, Yoke-Lin School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia
- Marques, Remedios Department of Pharmacy Services, La Fe Hospital, Valencia, Spain
- Peris, José-Esteban Department of Pharmacy and Pharmaceutical Technology, University of Valencia, Valencia, Spain
- Lutsar, Irja Institute of Medical Microbiology, University of Tartu, Tartu, Estonia
- Saito, Jumpei Department of Pharmacy, National Children’s Hospital National Center for Child Health and Development, Tokyo, Japan
- Nakamura, Hidefumi Department of Development Strategy, Center for Clinical Research and Development, National Center for Child Health and Development, Tokyo, Japan
- van den Anker, Johannes N Department of Paediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, Basel, Switzerland
- Sharland, Mike Paediatric Infectious Disease Unit, St George’s Hospital, London, UK
- Zhao, Wei ORCID Department of Clinical Pharmacy, School of Pharmaceutical Sciences, Shandong University, Jinan, China
- 2019-5-2
Published in:
- Journal of Antimicrobial Chemotherapy. - Oxford University Press (OUP). - 2019, vol. 74, no. 8, p. 2128-2138
English
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1093/jac/dkz158
- ISSN 0305-7453
- Persistent URL
- https://sonar.ch/global/documents/232021
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