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Levetiracetam pharmacokinetics and its covariates: proposal for optimal dosing in the paediatric population
  1. Pavla Pokorná1,2,3,4,
  2. Martin Šíma1,
  3. Natálie Švestková3,
  4. Ondřej Slanař1
  1. 1Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
  2. 2Department of Physiology and Pharmacology, Karolinska University Hospital, Stockholm, Sweden
  3. 3Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
  4. 4Intensive Care and Department of Pediatric Surgery, Erasmus University Medical Center – Sophia Children's Hospital, Rotterdam, Netherlands
  1. Correspondence to Dr Martin Šíma, Department of Pharmacology, First Faculty of Medicine, Charles University and General University Hospital in Prague, 128 00 Prague, Czech Republic; martin.sima{at}lf1.cuni.cz

Abstract

Objectives Levetiracetam is an anticonvulsive drug increasingly used in paediatric populations. Ontogenesis may alter its pharmacokinetics, demanding dose individualisation of levetiracetam in paediatric populations. We therefore aimed to explore levetiracetam pharmacokinetics and to propose its optimal dosing in the paediatric population.

Methods Individual levetiracetam pharmacokinetic parameters were calculated based on therapeutic drug monitoring data, using a one-compartmental model, and regression models were used to explore possible covariates.

Results 56 patients aged from 47 days to 18 years were included in the analysis. The median (IQR) volume of distribution and clearance of levetiracetam were 0.7 (0.58–0.85) L/kg and 0.123 (0.085–0.167) L/hour/kg, respectively. Levetiracetam pharmacokinetics were influenced by postnatal age, body size descriptors and renal functional status.

Conclusions Based on observed relationships, an individualised loading dose of 26.2 mg/kg body weight and maintenance dose of 20.7 mg/mL/min of estimated glomerular filtration rate were calculated as optimal. Since we observed increased levetiracetam clearance in association with valproate co-medication, caution should be used when combining these two drugs.

  • pharmacokinetics
  • therapeutic drug monitoring
  • pediatrics
  • drug monitoring
  • drug-related side effects and adverse reactions

Data availability statement

Data are available upon reasonable request. Not applicable.

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Data availability statement

Data are available upon reasonable request. Not applicable.

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