TY - JOUR
T1 - The effects of co-medications on lamotrigine clearance in Japanese children with epilepsy
AU - Takeuchi, Tomoya
AU - Natsume, Jun
AU - Kidokoro, Hiroyuki
AU - Ishihara, Naoko
AU - Yamamoto, Hiroyuki
AU - Azuma, Yoshiteru
AU - Ito, Yuji
AU - Kurahashi, Naoko
AU - Tsuji, Takeshi
AU - Suzuki, Motomasa
AU - Itomi, Kazuya
AU - Yamada, Keitaro
AU - Kurahashi, Hirokazu
AU - Abe, Shinpei
AU - Okumura, Akihisa
AU - Maruyama, Koichi
AU - Negoro, Tamiko
AU - Watanabe, Kazuyoshi
AU - Kojima, Seiji
N1 - Publisher Copyright:
© 2016 The Japanese Society of Child Neurology
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.braindev.2016.03.004
DO - 10.1016/j.braindev.2016.03.004
M3 - Article
C2 - 27033151
AN - SCOPUS:84991340880
SN - 0387-7604
VL - 38
SP - 723
EP - 730
JO - Brain and Development
JF - Brain and Development
IS - 8
ER -