title: A pharmacokinetic study and correlation with clinical response of rufinamide in infants with epileptic encephalopathies.
abstract: OBJECTIVE
  To evaluate the relationship between the pharmacokinetic (PK) parameters and therapeutic and adverse effects of rufinamide (RUF) in children with epileptic encephalopathies (EE) aged <4 years.
  
  
  METHODS
  PK analysis was conducted at the steady state using a previously validated liquid chromatography tandem-mass spectrometric method in 15 children aged 6-42 months treated with RUF in add-on. Responders were defined as patients who achieved >50% decrease of seizures. Tolerability was evaluated by analysis of a parental report of adverse effects, a clinical examination and laboratory tests.
  
  
  RESULTS
  Maximum plasma concentration (47.40 ± 35.36 mg/l), average plasma concentration (39.94 ± 24.53 mg/l) and half-life (13.66 ± 4.43 h) were extremely variable and considerably higher than those reported in older children treated with the same dose regimen. At the last evaluation, 9 patients (60%) were responders.
  
  
  CONCLUSIONS
  RUF is efficacious and is well tolerated in children with EE. Nonetheless, a correlation between dose, serum concentration and efficacy could not be demonstrated. The variability in measured concentrations may be related to polytherapy that is necessary for controlling seizures in this very severe form of epilepsy, in which the off-label use of RUF is justified.
authors.affiliation: Newborn Screening, Clinical Chemistry and Pharmacology Laboratory, Florence, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Anna
authors.initials: A
authors.lastname: Rosati
authors.forename: Melania
authors.initials: M
authors.lastname: Falchi
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Della Bona
authors.forename: Simona
authors.initials: S
authors.lastname: Pellacani
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
mesh_terms: D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000097:blood* / Q000188:drug therapy; D065768:Lennox Gastaut Syndrome; D008297:Male; D013036:Spasms, Infantile / Q000097:blood* / Q000188:drug therapy; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014230:Triazoles; C079703:rufinamide