Developmental and Therapeutic Pharmacology of Antiepileptic Drugs

唑尼沙胺（ZNS）是日本开发的一种新型抗癫痫药物。它从胃肠道吸收缓慢，与其他流行的抗癫痫药物相比，其生物半衰期较长。我们研究了ZNS和卡马西平（CBZ）在隐源性定位相关癫痫患儿中的药物相互作用，这些患儿的癫痫发作不能通过每日一次的ZNS单药治疗来控制，尽管保持高血浆水平。12例患者年龄5 ~ 16岁（平均12岁1个月），先用ZNS治疗，再加用CBZ治疗。经ZNS与CBZ联合治疗后，12例患者中有9例改为CBZ单药治疗。ZNS每天早晨1次服食。在早晨给药前和4小时后分别取血样测定血浆浓度，分别代表一天中的波谷和峰值水平。CBZ每天分两次给药。12例患者在ZNS单药治疗中加入CBZ日剂量15.1<正负>3.0mg/kg（11.1<正负>2.5mg/kg/day）后，ZNS波谷和波峰水平分别从35.4<正负>10.0降至22.2<正负>9.8 mg/ ml和43.0<正负>11.3降至28.1<正负>12.5 mg/ ml。晨给药前CBZ及其主要代谢物卡马西平-10,11-环氧化物（carbamazepin-10,11-epoxide, CBZ- e）血浆水平分别为6.05<正负>1.98和1.32<正负>0.23mug/ml，晨给药后4 h CBZ血浆水平分别为9.06<正负>2.83和1.61<正负>0.35mug/ml。另一方面，9例由合并用药改为合并用药的患者，无论是单独使用CBZ还是联合使用ZNS，血浆中ZNS浓度均无显著差异，同时使用CBZ可降低血浆中ZNS浓度，但ZNS对CBZ和CBZ- e均无影响。

Zonisamide (ZNS) is a new antiepileptic drug developed in Japan. It is absorbed slowly from the gastrointestinal tract, and its biological half-life is long as compared with those of other prevalent antiepileptic drugs. We investigated drug interaction between ZNS and carbamazepine (CBZ) in children with cryptogenic localization-related epilepsies whose seizures were not controlled by a once-daily dose of ZNS monotherapy, despite maintaining high plasma levels.Twelve patients aged 5 to 16 (mean, 12 years and 1 month) were first treated with ZNS alone, CBZ was thenadded. After combination therapy with ZNS and CBZ,drug therapy was changed to CBZ monotherapy in 9 of the 12 patients. ZNS was ingested once a day in the morning. Blood samples for determination of plasma concentrations were taken before and 4 hours after the morning dose, each representing the trough and peak levels in a day. CBZ was prescribed in two divided doses per day.When the daily dosage of 15.1<plus-minus>3.0mg/kg of CBZ was added to ZNS monotherapy (11.1<plus-minus>2.5mg/kg/day) in 12 patients, trough and peak levels of ZNS decreased from 35.4<plus-minus>10.0 to 22.2<plus-minus>9.8mug/ml and 43.0<plus-minus>11.3 to 28.1<plus-minus>12.5mug/ml, respectively. Plasma levels of CBZ and its main metabolite carbamazepin-10,11-epoxide (CBZ-E) before the morning dose were 6.05<plus-minus>1.98 and 1.32<plus-minus>0.23mug/ml, and those 4 hours after the morning dose were 9.06<plus-minus>2.83 and 1.61<plus-minus>0.35mug/ml, respectively. On the other hand, there were no significant differences in plasma levels of CBZ nor CBZ-E,whether CBZ was used alone or combined with ZNS in 9 patients in whom drug therapy was changed from combination with CBZ and ZNSConcurrent administration of CBZ decreases plasma concentrations of ZNS,but ZNS has no effect on plasma concentrations of both CBZ and CBZ-E.