Developmental Pharmacology and Therapeutic Drug Monitoring of Antiepileptic Drugs

在一项前瞻性随机研究中，我们调查了在接受丙戊酸钠（VPA）单药治疗的儿童中癫痫大发作的长期结局。患者包括194名未接受治疗的儿童，年龄8个月至15岁（平均8岁1个月），他们是新转介到我们的儿科癫痫诊所的。给予VPA 25 ~ 30 mg/kg日剂量，初始维持日剂量（27.0±3.6mg/kg）时血浆水平为103.1±1 8.2μg/ml。在194例患者中，有16例患者的癫痫发作未被VPA单药控制，58例患者在治疗过程中失去随访。在剩余的120例患者中，有108例VPA单药治疗平均持续5年零8个月，然后停止药物治疗。87例患者成功停药，停药后随访6个月至15年（平均7年4个月）无癫痫复发。然而，在其他21例患者中，癫痫发作在停止治疗后2周至4年（平均7个月）复发。停药后癫痫复发与无复发患者的疗程差异无统计学意义，但9岁以后发病患者的复发率明显高于对照组（17/43=39.5%）。在儿童期至青春期的治疗过程中，在相同的维持日剂量下，血浆VPA浓度下降了约20%。VPA单药治疗癫痫患儿醒后大发作的远期疗效良好，但对老年患者停药后癫痫发作的复发应引起注意。

We investigated the long-term outcome of epilepsy with grand mal seizures on awakening in a prospective randomized study in children who were treated with sodium valproate (VPA) monotherapy.The patients comprised 194 previously untreated children aged 8 months to 15 years (mean, 8 years 1 month), who had been newly referred to our pediatric seizure clinic. A daily dose of 25-30 mg/kg of VPA was introduced, and the initial maintenance daily dosage of VPA (27.0±3.6mg/kg) gave the plasma levels of 103.1±1 8.2μg/ml.Of the total 194 patients, seizures were not controlled in 16 by VPA monotherapy, and 58 patients were lost from follow-up during the course of treatment. In 108 out of the remaining 120 patients, VPA monotherapy was continued for a mean of 5 years and 8 months, and then the drug therapy was discontinued. The drug therapy was successfully discontinued in 87, in whom no seizure recurrences were ocurred during the follow-up period 6 months to 15 years (mean, 7 years 4 months) after stopping the therapy. However, in the other 21 patients seizures recurred 2 weeks to 4 years (mean, 7 months) after stopping the therapy. There were no differences in the course of treatment between the cases with seizure recurrences and those without recurrences after discontinuance of the therapy, but the recurrence rate was significantly higher in the patients who were taken ill after the age of 9 (17/43=39.5%). During the course of treatment from childhood to adolescence on the same maintence daily dosage, the plasma concentrations of VPA showed a decrease of about 20%.The long-term outcome of epileptic children with grand mal seizures on awakening treated with VPA monotherpy is excellent, but the attention should be paid for the recurrence of seizures after stopping therapy in the cases of older patient.