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Scientific article
English

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

Published inThe journal of antimicrobial chemotherapy, vol. 77, no. 2, p. 457-465
Publication date2022-02-01
First online date2021-11-17
Abstract

Objectives

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.

Methods

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).

Results

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).

Conclusions

Dosing adjustment according to BW, GA and PNA optimizes imipenem exposure in neonates.

eng
Keywords
  • Pharmacometric model
  • Drug dose regimen
  • Simulation
Citation (ISO format)
DAO, Kim et al. Dosing strategies of imipenem in neonates based on pharmacometric modelling and simulation. In: The journal of antimicrobial chemotherapy, 2022, vol. 77, n° 2, p. 457–465. doi: 10.1093/jac/dkab394
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ISSN of the journal0305-7453
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