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

Jacqz-Aigrain, Evelyne and Leroux, Stephanie and Thomson, Alison H. and Allegaert, Karel and Capparelli, Edmund V. and Biran, Valerie 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

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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.

    Author(s):Jacqz-Aigrain, Evelyne, Leroux, Stephanie, Thomson, Alison H. ORCID logoORCID: https://orcid.org/0000-0002-2354-6116, Allegaert, Karel, Capparelli, Edmund V., Biran, Valerie, 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 and Zhao, Wei
    Item type:Article
    ID code:69955
    Keywords:vancomycin, steady state, drug loading dose, drug maintenance dose, creatinine tests, infusion procedures, Pharmacy and materia medica, Infectious Diseases, Pharmacology, Pharmacology (medical)
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:25 Sep 2019 10:41
    Last modified:06 Nov 2019 04:14
    URI:https://strathprints.strath.ac.uk/id/eprint/69955
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