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BMC Neurology
Published in: BMC Neurology 1/2024

Open Access 01-12-2024 | Levetiracetam | Research

Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance

Authors: Aaron M. Cook, Kaylee Hall, Jimmi Hatton Kolpek, Kathryn A. Morbitzer, J. Dedrick Jordan, Denise H. Rhoney

Published in: BMC Neurology | Issue 1/2024

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Abstract

Background

The purpose of this study was to examine the impact of ARC on levetiracetam concentrations during the first week following acute TBI. The hypothesis was levetiracetam concentrations are significantly lower in TBI patients with augmented renal clearance (ARC) compared to those with normal renal clearance.

Methods

This is a prospective cohort pharmacokinetic study of adults with moderate to severe TBI treated with levetiracetam during the first week after injury. Serial blood collections were performed daily for analysis of levetiracetam, cystatin C, and 12-hr creatinine clearance (CrCl) determinations. Patients were divided into two cohorts: with (CrCl ≥130 ml/min/1.73 m2) and without ARC.

Results

Twenty-two patients with moderate to severe TBI were included. The population consisted primarily of young male patients with severe TBI (mean age 40 years old, 68% male, median admission GCS 4). Each received levetiracetam 1000 mg IV every 12 h for the study period. ARC was present in 77.3% of patients, with significantly lower levetiracetam concentrations in ARC patients and below the conservative therapeutic range (< 6mcg/mL) for all study days. In patients without ARC, the serum concentrations were also below the expected range on all but two study days (Days 4 and 5). Four of the 22 (18.2%) patients exhibited seizure activity during the study period (two of these patients exhibited ARC). Cystatin C concentrations were significantly lower in patients with ARC, though the mean for all patients was within the typical normal range.

Conclusions

ARC has a high prevalence in patients with moderate to severe TBI. Levetiracetam concentrations after standard dosing were low in all TBI patients, but significantly lower in patients with ARC. This study highlights the need to consider personalized drug dosing in TBI patients irrespective of the presence of ARC.

Clinical trial registration

This study was registered at cliicaltrials.gov (NCT02437838) Registered on 08/05/2015, https://​clinicaltrials.​gov/​ct2/​show/​NCT02437838.
Appendix
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Metadata
Title
Enhanced renal clearance impacts levetiracetam concentrations in patients with traumatic brain injury with and without augmented renal clearance
Authors
Aaron M. Cook
Kaylee Hall
Jimmi Hatton Kolpek
Kathryn A. Morbitzer
J. Dedrick Jordan
Denise H. Rhoney
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2024
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-023-03515-w

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