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A pharmacokinetic study and correlation with clinical response of rufinamide in infants with epileptic

Giancarlo la Marca1, Anna Rosati, Melania Falchi

  • 1Newborn Screening, Clinical Chemistry and Pharmacology Laboratory, Florence, Italy.

Pharmacology
|May 29, 2013
PubMed

Insights

Rufinamide (RUF) is effective and well-tolerated in young children with epileptic encephalopathies (EE). However, high variability in rufinamide concentrations was observed, with no clear link between dose, concentration, and seizure reduction.

Area of Science:

  • Pharmacology and Therapeutics
  • Pediatric Neurology
  • Epilepsy Research

Background:

  • Epileptic encephalopathies (EE) in children under 4 years present significant treatment challenges.
  • Rufinamide (RUF) is an antiepileptic drug, but its use in very young children requires careful pharmacokinetic evaluation.
  • Understanding the relationship between RUF pharmacokinetics and clinical outcomes is crucial for optimizing treatment in this vulnerable population.

Purpose of the Study:

  • To assess the pharmacokinetic (PK) parameters of rufinamide (RUF) in children under 4 years with epileptic encephalopathies (EE).
  • To evaluate the correlation between RUF PK parameters and both therapeutic efficacy and adverse effects.
  • To determine the tolerability and efficacy of rufinamide as an add-on therapy in this specific pediatric population.

Main Methods:

  • Pharmacokinetic (PK) analysis was performed at steady state in 15 children (6-42 months) receiving add-on rufinamide.
  • A validated liquid chromatography tandem-mass spectrometric method was used for drug concentration measurements.
  • Therapeutic response was defined as >50% seizure reduction, and tolerability was assessed via parental reports, clinical exams, and lab tests.

Main Results:

  • Rufinamide plasma concentrations (Cmax, Cav) and half-life were highly variable and higher than in older children on the same dose.
  • Sixty percent (9 out of 15) of the children achieved a >50% reduction in seizures, indicating treatment efficacy.
  • Despite variability, rufinamide was generally well-tolerated, with no significant adverse events reported that precluded its use.

Conclusions:

  • Rufinamide demonstrates efficacy and good tolerability in young children with severe epileptic encephalopathies.
  • A direct correlation between rufinamide dose, serum concentration, and seizure control could not be established in this cohort.
  • The observed variability in rufinamide concentrations may be influenced by polytherapy, justifying the off-label use of RUF in these severe epilepsy cases.
Abstract

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