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194例既往未接受过治疗的儿童，年龄8个月至15岁（平均8岁1个月），这些儿童接受了丙戊酸钠（VPA）单药治疗，他们是新近转诊到我们的儿科癫痫发作门诊的。VPA的初始维持剂量为27.0±3.6mg/kg/d，血药浓度为103.1± 18.2 μg/ml，194例患者中，16例VPA单药治疗后癫痫未得到控制，58例失访。在其余120例患者中，108例患者继续接受VPA单药治疗平均5年8个月，然后停止药物治疗。停药成功87例，停药后随访6个月~ 15年，平均7年4个月，无癫痫复发。另21例患者在停药后2周至4年（平均7个月）癫痫复发。停药后癫痫复发与未复发者的疗程无差异，但9岁以后发病的患者复发率明显增高（17/43=39.5%）。从儿童期到青春期，维持相同剂量的VPA治疗，其血药浓度下降约20%; VPA单药治疗儿童癫痫大发作的远期疗效较好，但对于年龄较大的患者，应注意停药后癫痫的复发。

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.