1. Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.
- 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, Anker, Johannes N van den, Sharland, Mike, Zhao, Wei, and van den Anker, Johannes N
- Subjects
MONTE Carlo method ,PREMATURE infants ,META-analysis ,NEWBORN infants ,INFANTS ,POPULATION ,DRUG dosage ,ANTIBIOTICS ,BODY weight ,CLINICAL trials ,COMPARATIVE studies ,DOSE-effect relationship in pharmacology ,EXPERIMENTAL design ,GESTATIONAL age ,RESEARCH methodology ,MEDICAL cooperation ,MICROBIAL sensitivity tests ,PHARMACOKINETICS ,RESEARCH ,STATISTICS ,SYSTEM analysis ,VANCOMYCIN ,DATA analysis ,EVALUATION research - 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. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
- View/download PDF