Takeuchi Tomoya, Natsume Jun, Kidokoro Hiroyuki, Ishihara Naoko, Yamamoto Hiroyuki, Azuma Yoshiteru, Ito Yuji, Kurahashi Naoko, Tsuji Takeshi, Suzuki Motomasa, Itomi Kazuya, Yamada Keitaro, Kurahashi Hirokazu, Abe Shinpei, Okumura Akihisa, Maruyama Koichi, Negoro Tamiko, Watanabe Kazuyoshi, Kojima Seiji
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Brain Dev. 2016 Sep;38(8):723-30. doi: 10.1016/j.braindev.2016.03.004. Epub 2016 Mar 28.
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.
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)).
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.
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.
虽然已有报道称一些抗癫痫药物对拉莫三嗪（LTG）清除率有诱导或抑制作用，但它们在亚洲癫痫患者中是否与在其他国家的患者有相同作用尚未明确，尤其是在儿童中。本研究的目的是确定联合用药对日本癫痫患儿LTG清除率的影响。
回顾了102名20岁以下日本癫痫患者共342次LTG常规血清浓度测量结果。LTG的剂量校正浓度（DCC）计算为[浓度]/[剂量/（体重）]，并通过联合用药比较LTG的DCC。比较了使用和未使用丙戊酸（VPA）的患者以及使用和未使用诱导葡萄糖醛酸结合的药物（苯妥英（PHT）、卡马西平（CBZ）和苯巴比妥（PB））的患者之间LTG的DCC差异。
与LTG单药治疗的患者相比，使用VPA的患者LTG的DCC显著更高，而使用诱导葡萄糖醛酸结合的药物的患者LTG的DCC显著更低。使用CBZ的患者LTG的DCC显著高于使用PHT或PB的患者。在治疗范围内，LTG的DCC与VPA或代谢诱导剂的浓度之间无相关性。包括氯巴占、氯硝西泮、唑尼沙胺和左乙拉西坦在内的其他抗癫痫药物对LTG浓度影响很小。
与其他国家先前报道的一样，在日本儿童中，LTG浓度会因联合使用抗癫痫药物而发生显著变化，需要特别关注。虽然在开始或停用VPA或代谢诱导剂时应调整LTG剂量，但在治疗范围内改变VPA或代谢诱导剂剂量时无需调整。
