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  • Population pharmacokinetic ...
    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

    Journal of antimicrobial chemotherapy, 08/2019, Letnik: 74, Številka: 8
    Journal Article

    In the absence of consensus, the present meta-analysis was performed to determine an optimal dosing regimen of vancomycin for neonates. 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. 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. 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.