title: Topiramate pharmacokinetics in infants.
abstract: OBJECTIVE
  This study's goal was to provide preliminary data on the pharmacokinetics of topiramate (TPM) in a cohort of infants (younger than 4 years) participating in an open-label trial of TPM in refractory infantile spasms.
  
  
  METHODS
  The pharmacokinetics of TPM were assessed in infants receiving a stable TPM dose for >7 days during the extension phase of this trial. Blood samples were drawn just before and 0.5. 1, 1.5, 2, 4, 6, 8, and 12 h after the morning TPM dose. TPM plasma concentrations were determined by fluorescence polarization immunoassay. The noncompartmental analysis module of WinNonlin was used to calculate individual patient pharmacokinetics profiles.
  
  
  RESULTS
  Five infants (ages, 23.5-29.5 months) formed the study cohort. These infants had been given TPM for a median of 9 months (range, 6-11 months) and were currently receiving between 11 and 38.5 mg/kg/day TPM. One was receiving TPM monotherapy, whereas four were taking concomitant antiepileptic medications (AEDs; n = 2, enzyme-inducing agents; n = 2, non-enzyme-inducing drugs). TPM pharmacokinetics in infants appears to be linear. In this cohort, mean TPM plasma clearance (CL/F, 66.6+/-27.4 ml/h/kg) was slightly higher than that reported for children and adolescents and therefore substantially higher than that reported for adults. TPM CL/F was higher and the calculated half-life shorter in the infants receiving concomitant enzyme-inducing AEDs.
  
  
  CONCLUSIONS
  Based on this small cohort of patients, it appears that infants may require significantly larger TPM doses, based on weight, than children, adolescents, or adults. Titration to effect and not absolute TPM dose should guide therapy in this age group.
authors.affiliation: Children's Comprehensive Epilepsy Program, Department of Neurology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Glauser
authors.forename: M V
authors.initials: MV
authors.lastname: Miles
authors.forename: P
authors.initials: P
authors.lastname: Tang
authors.forename: P
authors.initials: P
authors.lastname: Clark
authors.forename: K
authors.initials: K
authors.lastname: McGee
authors.forename: D R
authors.initials: DR
authors.lastname: Doose
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D005632:Fructose / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D013036:Spasms, Infantile / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D000077236:Topiramate
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose