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RESEARCH PRODUCT
Population pharmacokinetic meta-analysis of individual data to design the first randomized efficacy trial of vancomycin in neonates and young infants.
Evelyne Jacqz-aigrainJohannes N. Van Den AnkerAlison H. ThomsonAlison H. ThomsonStéphanie LerouxHidefumi NakamuraKarel AllegaertKarel AllegaertRemedios MarquesEdmund V. CapparelliIrja LutsarBernd MeibohmNicolas SimonJumpei SaitoValérie BiranMike SharlandJosé Esteban PerisWei ZhaoLo YlLo Ylsubject
0301 basic medicinePediatricsvancomycininfusion procedures0302 clinical medicinenewbornMedicinePharmacology (medical)Randomized Controlled Trials as Topiceducation.field_of_studyMaintenance doseAnti-Bacterial Agents3. Good healthInfectious Diseasesdrug maintenance doseResearch DesignArea Under CurveData Interpretation Statisticalcreatinine testsVancomycinMonte Carlo Methodmedicine.drugMicrobiology (medical)medicine.medical_specialty030106 microbiologyPopulationGestational AgeMicrobial Sensitivity TestsLoading doseRS03 medical and health sciencesPharmacokineticsdrug loading dose030225 pediatricsHumanssteady stateeducationPharmacologyDose-Response Relationship Drugbusiness.industryBody WeightInfant NewbornPostmenstrual AgeinfantNONMEMRegimen[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologieregimen[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologiebusinessserumdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-08-01 |