title: Effect of CYP2C19 polymorphisms on stiripentol administration in Japanese cases of Dravet syndrome.
abstract: OBJECTIVE
  The objective of this study was to investigate stiripentol (STP) administration in cases of Dravet syndrome (DS) by comparing CYP2C19 allelic polymorphisms with the clinical effects of STP, including plasma concentrations of concomitant drugs and adverse effects of STP.
  
  
  METHODS
  Eleven cases of DS cases were included. Demographic and clinical characteristics of the cases (age at the study period, body weight, mean dose and plasma concentration of valproate acid (VPA)/clobazam (CLB) off and on STP, mean plasma concentration of norclobazam (N-CLB) off and on STP, degree of seizure reduction, and adverse effects of STP) were examined with each CYP2C19 polymorphism.
  
  
  RESULTS
  There were 3 cases of DS with wild type, 6 with intermediate type, and 2 with poor type of CYP2C19 polymorphisms. The N-CLB concentration/CLB dose ratio and N-CLB/CLB concentration ratio off STP were significantly higher in poor metabolizers. Three (37%) of 8 cases showed no effectiveness of STP regardless of the N-CLB concentration increase, and 1 (33%) of 3 cases showed effectiveness of STP regardless of N-CLB concentration decrease. In total, 6 (54%) of 11 cases with DS had >50% reduction in seizure frequency without significant differences in CYP2C19 polymorphisms.
  
  
  CONCLUSIONS
  This study demonstrated an effect of CYP2C19 polymorphisms on STP administration in Japanese cases of DS. There were cases of seizure reduction regardless of N-CLB concentration decrease on STP, which suggests a significant anti-convulsant action of STP. N-CLB concentration decrease on STP was observed in 1 case with ketogenic diet and 2 cases with (∗)3 allelic polymorphisms of CYP2C19.
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kouga
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimbo
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Mizue
authors.initials: M
authors.lastname: Iai
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.affiliation: Departments of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Departments of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ihara
authors.affiliation: Departments of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan; Central Research Institute for the Pathomechanisms of Epilepsy, Fukuoka University, Fukuoka, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Division of Neurology, Kanagawa Children's Medical Center, Yokohama, Japan; Department of Pediatrics, Jichi Medical University, Shimotsuke, Japan. Electronic address: hosaka@jichi.ac.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Osaka
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D004148:Dioxolanes / Q000627:therapeutic use*; D004831:Epilepsies, Myoclonic / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D000927:Anticonvulsants; D004148:Dioxolanes; D065731:Cytochrome P-450 CYP2C19; C021092:stiripentol
keywords: CYP2C19 polymorphisms; Clobazam; Dravet syndrome; Norclobazam; Stiripentol