The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy

Tomoya Takeuchi, Jun Natsume, Hiroyuki Kidokoro, Naoko Ishihara, Hiroyuki Yamamoto, Yoshiteru Azuma, Yuji Ito, Naoko Kurahashi, Takeshi Tsuji, Motomasa Suzuki, Kazuya Itomi, Keitaro Yamada, Hirokazu Kurahashi, Shinpei Abe, Akihisa Okumura, Koichi Maruyama, Tamiko Negoro, Kazuyoshi Watanabe, Seiji Kojima

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Purpose 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 20 years 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. Conclusion 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.

Original languageEnglish
Pages (from-to)723-730
Number of pages8
JournalBrain and Development
Volume38
Issue number8
DOIs
Publication statusPublished - 01-09-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

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