Developmental and Therapeutic Pharmacology of Antiepileptic Drugs

1.在未接受其他抗惊厥药物治疗的患者中，研究了丙戊酸钠（VPA）与卡马西平（CBZ）同时给药对卡马西平、卡马西平-10，11-环氧化物（CBZ-E）及其二醇代谢物10，11-二羟基卡马西平（CBZ-H）稳态血药浓度的影响。CBZ被广泛代谢为活性代谢物CBZ-E，最后代谢为无活性的CBZ-H。我们的研究表明，CBZ和VPA同时治疗的患者中CBZ-E的血浆水平和CBZ-E/CBZ比显著高于单独使用CBZ治疗的患者，而血浆CBZ-H/CBZ-同时应用VPA可使CBZ和CBZ-E的游离分数升高。因此，相对于CBZ剂量，同时给予VPA增加了总血浆CBZ-E水平，与CBZ和CBZ-E的游离分数升高相关。高浓度血浆CO 关于我们 CBZ-E的浓度可能是导致某些患者副作用的原因.目的观察唑尼沙胺（ZNS）单药治疗儿童隐源性定位相关性癫痫的临床疗效和血药浓度。ZNS在胃肠道吸收缓慢，生物半衰期较其他抗癫痫药物长。在早晨给药前和给药后4小时采集用于测定血浆水平的血样，每个血样代表一天中的谷值和峰值水平，峰谷血浆水平比小至约1.25。通过血浆谷值和峰值水平估计的血浆水平（mug/m2）与剂量（mg/kg/天）比值均随年龄增长而增加。患者的临床效果与普遍接受的ZNS治疗血药浓度范围一致，即15- 40 μ g/ml。同时给予CBZ降低了大多数患者的ZNS血药浓度，尽管ZNS维持了高血药浓度，但每日一次剂量的ZNS单药治疗仍不能控制癫痫发作。少

1. The influence of concurrently administered sodium valproate (VPA) on the steady-state plasma concentrations of carbamazepine (CBZ), carbamazepine-10, 11-epoxide (CBZ-E) and its diol metabolite 10, 11-dihydroxycarbamazepine (CBZ-H) was investigated in patients receiving CBZ together with VPA, who received no other anticonvulsants. CBZ is extensively metabolized to the active metabolite CBZ-E and finally to the inactive CBZ-H.Our study showed that the plasma levels of CBZ-E and CBZ-E/CBZ ratio were significantly higher in the patients treated concurrently with CBZ and VPA than in those treated with CBZ alone, whereas the plasma CBZ-H/CBZ-E ratio was significantly lower in the former group.It was shown also that the concurrent administration of VPA raises the free fraction of both CBZ and CBZ-E. Consequently, a simultaneous administration of VPA increases the total plasma CBZ-E level relative to the CBZ dose, associated with the raised free fraction of CBZ and CBZ-E. The high plasma co … More ncentration of CBZ-E may be responsible for the side effects in some patients.2. The clinical effects and plasma levels of zonisamide (ZNS) were investigated in children with cryptogenic localization-related epilepsies, who were administered ZNS once a day as a single drug. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long compared with the other prevalent antiepileptic drugs. Blood samples for determination of plasma levels were taken before and 4 hours after the morning dose, each of which represents the trough and peak levels in a day.The peak to trough plasma level ratios were as small as approximately 1.25. The plasma level (mug/m) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels increased both with advance in age. The clinical effects in the patients were in agreement with the range of generally accepted therapeutic plasma levels of ZNS, that is 15-40mug/ml.The concurrent administration of CBZ decreased the plasma concentrations of ZNS in most of the patients, whose seizures were not controlled by once-daily dose of ZNS monotherapy, in spite of maintaining the high plasma levels. Less