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Levetiracetam pharmacokinetics and its covariates: proposal for optimal dosing in the paediatric population

Pavla Pokorná1,2,3,4, Martin Šíma5, Natálie Švestková3

  • 1Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

European Journal of Hospital Pharmacy : Science and Practice
|November 10, 2021
PubMed

Insights

Optimizing levetiracetam dosing in children is crucial due to pharmacokinetic changes during development. This study proposes individualized loading and maintenance doses based on patient factors for better seizure control.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Clinical Pharmacy

Background:

  • Levetiracetam is a widely used anticonvulsant in pediatric patients.
  • Drug pharmacokinetics can change significantly during childhood development (ontogenesis).
  • Individualized dosing is necessary to ensure optimal levetiracetam efficacy and safety in children.

Purpose of the Study:

  • To investigate the pharmacokinetics of levetiracetam in pediatric populations.
  • To develop an optimal dosing strategy for levetiracetam in children.

Main Methods:

  • Analyzed therapeutic drug monitoring data from 56 pediatric patients (47 days to 18 years).
  • Utilized a one-compartmental model to calculate individual pharmacokinetic parameters.
  • Employed regression models to identify influencing covariates on levetiracetam pharmacokinetics.

Main Results:

  • Levetiracetam pharmacokinetics were significantly affected by postnatal age, body size, and renal function.
  • Median volume of distribution was 0.7 L/kg and median clearance was 0.123 L/hour/kg.
  • Co-administration with valproate was associated with increased levetiracetam clearance.

Conclusions:

  • Individualized loading dose of 26.2 mg/kg and maintenance dose of 20.7 mg/mL/min GFR are recommended.
  • Dosing adjustments are essential based on patient-specific factors like age and renal status.
  • Caution is advised when co-administering levetiracetam with valproate due to altered clearance.
Abstract

Keywords:
drug monitoringdrug-related side effects and adverse reactionspediatricspharmacokineticstherapeutic drug monitoring

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