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

Fecha de publicación: 01/08/2019

Autores de IIS La Fe

María Remedios Marques Miñana

Autor

Participantes ajenos a IIS La Fe

Jacqz-Aigrain, E
Leroux, S
Thomson, AH
Allegaert, K
Capparelli, EV
Biran, V
Simon, N
Meibohm, B
Lo, YL
Peris, JE
Lutsar, I
Saito, J
Nakamura, H
van den Anker, JN
Sharland, M
Zhao, W

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 AUC(0-24) of 400mg.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 AUC(0-24) 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.

Datos de la publicación

ISSN/ISSNe:: 0305-7453, 1460-2091
Tipo:: Article
Páginas:: 2128-2138
DOI:: 10.1093/jac/dkz158
Factor de Impacto:: 2,230 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Jacqz-Aigrain, E:: Hop Robert Debre, AP HP, Dept Pediat Pharmacol & Pharmacogenet, Paris, France

Hop Robert Debre, Clin Invest Ctr CIC1426, Paris, France

Univ Paris Diderot, Sorbonne Paris Cite, Paris, France
Leroux, S:: Hop Robert Debre, AP HP, Dept Pediat Pharmacol & Pharmacogenet, Paris, France

Hop Robert Debre, Clin Invest Ctr CIC1426, Paris, France

CHU Rennes, Dept Child & Adolescent Med, Div Neonatol, Rennes, France
Thomson, AH:: Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland

Glasgow Royal Infirm, Pharm Dept, Glasgow, Lanark, Scotland
Allegaert, K:: Katholieke Univ Leuven, Dept Dev & Regenerat, Leuven, Belgium

Erasmus MC, Sophia Childrens Hosp, Intens Care, Rotterdam, Netherlands
Capparelli, EV:: Univ Calif San Diego, Pediat Pharmacol & Drug Discovery, San Diego, CA 92103 USA
Biran, V:: Hop Robert Debre, Neonatal Intens Care Unit, Paris, France
Simon, N:: Univ Mediterranee, Hop Timone, AP HM, Dept Pharmacol, Marseille, France

Hop Sainte marguerite, Serv Pharmacol Clin, CAP TV, F-13274 Marseille, France

Aix Marseille Univ, INSERM, SESSTIM, IRD, Marseille, France
Meibohm, B:: Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, Memphis, TN 38163 USA
Lo, YL:: Univ Malaya, Fac Med, Dept Pharm, Kuala Lumpur, Malaysia

Int Med Univ, Sch Pharm, Kuala Lumpur, Malaysia
Marques, R:: La Fe Hosp, Dept Pharm Serv, Valencia, Spain
Peris, JE:: Univ Valencia, Dept Pharm & Pharmaceut Technol, Valencia, Spain
Lutsar, I:: Univ Tartu, Inst Med Microbiol, Tartu, Estonia
Saito, J:: Natl Childrens Hosp, Natl Ctr Child Hlth & Dev, Dept Pharm, Tokyo, Japan
Nakamura, H:: Natl Ctr Child Hlth & Dev, Ctr Clin Res & Dev, Dept Dev Strategy, Tokyo, Japan
van den Anker, JN:: Glasgow Royal Infirm, Pharm Dept, Glasgow, Lanark, Scotland

Childrens Natl Med Ctr, Div Clin Pharmacol, Washington, DC 20010 USA

George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA

George Washington Univ, Sch Med & Hlth Sci, Dept Pharmacol & Physiol, Washington, DC 20052 USA

Univ Childrens Hosp Basel, Dept Paediat Pharmacol & Pharmacometr, Basel, Switzerland
Sharland, M:: St George Hosp, Paediat Infect Dis Unit, London, England