Dosing strategies of imipenem in neonates based on pharmacometric modelling and simulation.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_6EBEF14704F8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Dosing strategies of imipenem in neonates based on pharmacometric modelling and simulation.
Périodique
The Journal of Antimicrobial Chemotherapy
Auteur⸱e⸱s
Dao K., Fuchs A., André P., Giannoni E., Decosterd L.A., Marchetti O., Asner S.A., Pfister M., Widmer N., Buclin T., Csajka C., Guidi M.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Statut éditorial
Publié
Date de publication
02/02/2022
Peer-reviewed
Oui
Volume
77
Numéro
2
Pages
457-465
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Imipenem is a broad-spectrum antibacterial agent used in critically ill neonates after failure of first-line treatments. Few studies have described imipenem disposition in this population. The objectives of our study were: (i) to characterize imipenem population pharmacokinetics (PK) in a cohort of neonates; and (ii) to conduct model-based simulations to evaluate the performance of six different dosing regimens aiming at optimizing PK target attainment.
A total of 173 plasma samples from 82 neonates were collected over 15 years at the Lausanne University Hospital, Switzerland. The majority of study subjects were preterm neonates with a median gestational age (GA) of 27 weeks (range: 24-41), a postnatal age (PNA) of 21 days (2-153) and a body weight (BW) of 1.16 kg (0.5-4.1). PK data were analysed using non-linear mixed-effect modelling (NONMEM).
A one-compartment model best characterized imipenem disposition. Population PK parameters estimates of CL and volume of distribution were 0.21 L/h and 0.73 L, with an interpatient variability (CV%) of 20.1% on CL in a representative neonate (GA 27 weeks, PNA 21 days, BW 1.16 kg, serum creatinine, SCr 46.6 μmol/L). GA and PNA exhibited the greatest impact on PK parameters, followed by SCr. These covariates explained 36% and 15% of interindividual variability in CL, respectively.Simulated regimens using a dose of 20-25 mg/kg every 6-12 h according to postnatal age led to the highest PTA (T>MIC over 100% of time).
Dosing adjustment according to BW, GA and PNA optimizes imipenem exposure in neonates.
Mots-clé
Anti-Bacterial Agents, Computer Simulation, Critical Illness, Gestational Age, Humans, Imipenem, Infant, Infant, Newborn
Pubmed
Web of science
Création de la notice
19/11/2021 23:15
Dernière modification de la notice
12/07/2024 7:03
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