Authors
Léo Mimram, Moreno Ursino, Julie Leger, Emilie Bourrel-Ponchel, Florence Flamein, Alexandra Chadie, Isabelle Guellec, Sarah Zohar, Vincent Jullien, Géraldine Favrais
Published in
British journal of clinical pharmacology. Oct 20, 2026. Epub Oct 20, 2026.
Abstract
This study aimed to describe the pharmacokinetics (PK) of levetiracetam (LEV) in term neonates treated for neonatal seizures secondary to hypoxic-ischemic encephalopathy (HIE).
Fifteen neonates were included and received a loading dose ranging from 30 to 60 mg/kg followed by eight maintenance doses corresponding to one-fourth of the loading dose every 8 h. Five blood PK samples were drawn for each neonate: three after the loading dose and two after the last maintenance dose. Data were analysed by a population approach using NONMEM software. The possible relationship between LEV Cmax and AUC from time 0 to 4 h after the loading dose (AUC4h) and the relative seizure difference (RSD) that defined the LEV efficacy was investigated by linear regression.
LEV PK was described by a two-compartment model with allometric scaling based on body weight. Typical values (%IIV) for LEV CL, central and peripheral distribution volume (Vc and Vp) and distribution clearance (Q) were 4.27 (15%) L/h, 46.5 (14%) L, 6.10 L (98%) and 1.75 L/h, respectively. Creatinine clearance (CLcr) and natremia were found to be significant covariates for LEV clearance (CL), CL increasing with CLcr and natremia. No relationship was found between LEV Cmax or AUC4h and RSD.
A population PK model of LEV in term neonates with HIE was developed. The influence of natremia was highlighted for the first time and could reflect the relationship between the encephalopathy severity and LEV PK in this population.
PMID:
42902502
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.
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