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

Details

Serval ID
serval:BIB_6EBEF14704F8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dosing strategies of imipenem in neonates based on pharmacometric modelling and simulation.
Journal
Journal of Antimicrobial Chemotherapy
Author(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
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
77
Number
2
Pages
457-465
Language
english
Notes
Publication types: Journal Article
Publication Status: aheadofprint
Abstract
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.
Pubmed
Create date
19/11/2021 23:15
Last modification date
22/03/2022 7:34
Usage data