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Topiramate pharmacokinetics in infants and young children: contribution of population analysis

Marion Bouillon-Pichault1, Rima Nabbout, Stephanie Chhun

  • 1Inserm, U663, Paris F-75015, France. marion.bp@svp.aphp.fr

Epilepsy Research
|January 25, 2011
PubMed

Insights

Topiramate (TPM) dosing in young children requires careful consideration, especially when using enzyme-inducing antiepileptic drugs (EIAEDs). Alternative regimens may be needed to achieve therapeutic topiramate concentrations comparable to adults.

Area of Science:

  • Pharmacology
  • Pediatric Neurology
  • Drug Metabolism

Background:

  • Topiramate (TPM) is an antiepileptic drug used in children.
  • Understanding TPM pharmacokinetics in children under 4 is crucial for effective treatment.
  • Current recommended dosages may not consistently achieve target therapeutic ranges in this age group.

Purpose of the Study:

  • To determine topiramate (TPM) concentrations in children under 4 using the recommended dosage regimen (3-9 mg/kg/day).
  • To compare these concentrations to established adult target ranges.
  • To evaluate the impact of enzyme inducer antiepileptic drugs (EIAEDs) on TPM concentrations.

Main Methods:

  • Utilized a population pharmacokinetic model for TPM in children.
  • The model accounted for the presence or absence of EIAEDs.
  • Determined dosage regimens to achieve adult target ranges for area under the curve (AUC) and trough concentrations (C(trough)s).

Main Results:

  • TPM pharmacokinetics followed a one-compartment model.
  • EIAEDs significantly increased TPM clearance and decreased AUC and C(trough).
  • A dosage of 6-16 mg/kg/day, adjusted for age, was most likely to achieve target C(trough) ranges.

Conclusions:

  • A TPM dosage of 2 mg/kg/day (without EIAEDs) or 4 mg/kg/day (with EIAEDs) achieves adult AUC levels.
  • Alternative dosing strategies are recommended for children under 4, particularly when co-administered with EIAEDs, to reach adult C(trough) values.
Abstract

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