title: The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy.
abstract: OBJECTIVE
  Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy.
  
  
  METHODS
  A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed. The dose-corrected concentration (DCC) of LTG was calculated as [concentration]/[dose/(body weight)], and the DCC of LTG was compared by co-medication. The difference in the DCC of LTG was compared between patients with and without valproic acid (VPA) and between those with and without drugs inducing glucuronic acid conjugation (phenytoin (PHT), carbamazepine (CBZ), and phenobarbital (PB)).
  
  
  RESULTS
  The DCC of LTG was significantly higher in patients on VPA and significantly lower in patients on drugs inducing glucuronic acid conjugation than in patients on LTG monotherapy. The DCC of LTG was significantly higher in patients on CBZ than in patients on PHT or PB. There was no correlation between the DCC of LTG and the concentration of VPA or metabolic inducers within the therapeutic range. Other antiepileptic drugs including clobazam, clonazepam, zonisamide, and levetiracetam had little effect on LTG concentration.
  
  
  CONCLUSIONS
  LTG concentration changes dramatically with concomitant antiepileptic drugs in Japanese children, as previously reported from other countries, and special attention is required. Although the dose of LTG should be adjusted when starting or discontinuing VPA or metabolic inducers, no adjustment is needed when changing the dose of VPA or metabolic inducers in the therapeutic range.
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: tmtakeuchi-nagoya@umin.net.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Natsume
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kidokoro
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishihara
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Azuma
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kurahashi
authors.affiliation: Department of Pediatrics, Okazaki City Hospital, Okazaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsuji
authors.affiliation: Aichi Children's Health and Medical Center, Ohbu, Japan.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Aichi Children's Health and Medical Center, Ohbu, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Itomi
authors.affiliation: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kurahashi
authors.affiliation: Department of Pediatrics, Juntendo University Hospital, Tokyo, Japan.
authors.forename: Shinpei
authors.initials: S
authors.lastname: Abe
authors.affiliation: Department of Pediatrics, Juntendo University Hospital, Tokyo, Japan.
authors.forename: Akihisa
authors.initials: A
authors.lastname: Okumura
authors.affiliation: Department of Pediatric Neurology, Central Hospital, Aichi Human Service Center, Kasugai, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Maruyama
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Tamiko
authors.initials: T
authors.lastname: Negoro
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; Faculty of Health and Medical Sciences, Aichi Shukutoku University, Nagakute, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001569:Benzodiazepines / Q000008:administration & dosage; D002220:Carbamazepine / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D000078306:Clobazam; D002998:Clonazepam / Q000008:administration & dosage; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007555:Isoxazoles / Q000008:administration & dosage; D007564:Japan; D000077213:Lamotrigine; D000077287:Levetiracetam; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage; D010672:Phenytoin / Q000008:administration & dosage; D010889:Piracetam / Q000008:administration & dosage / Q000031:analogs & derivatives; D014227:Triazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014635:Valproic Acid / Q000008:administration & dosage; D055815:Young Adult; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D014227:Triazines; D001569:Benzodiazepines; D000078306:Clobazam; D002220:Carbamazepine; D000077287:Levetiracetam; D000078305:Zonisamide; D002998:Clonazepam; D014635:Valproic Acid; D010672:Phenytoin; D000077213:Lamotrigine; D010634:Phenobarbital; D010889:Piracetam
keywords: Child; Co-medication; Drug concentration; Drug interaction; Epilepsy; Lamotrigine