Visudtibhan Anannit, Bhudhisawadi Kasama, Vaewpanich Jarin, Chulavatnatol Suvatna, Kaojareon Sming
Division of Neurology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Brain Dev. 2011 Mar;33(3):189-94. doi: 10.1016/j.braindev.2010.04.003. Epub 2010 May 4.
Roles of intravenous administration of valproate in status epilepticus and serial seizures are documented in adults and children. Pharmacokinetic parameters are necessary to predict the optimum therapeutic level after administration. A cross-sectional study to determine the pharmacokinetic parameters and safety of intravenous valproate for future application was conducted in Thai children from January to December 2008. There were eleven children, age-range 1-15 years (mean age 9.5 years) enrolled. Valproate of 15-20 mg/kg was administrated intravenously at the rate of 3 mg/kg/min, followed by 6 mg/kg every 6 h. Valproate level was determined prior to the initial dose and at ½, 1, 2, 4, 5, and 6 h postdose. Complete blood count, serum ammonia, and liver function tests were collected prior to the initial dose and at 6 h. Median loading dose was 19 mg/kg (range 15-20.5 mg/kg). Median maximum concentration at 30 min after infusion was 98.8 mcg/mL (range 67-161 mcg/mL). Median volume of distribution was 0.20 L/kg (range 0.15-0.53 L/kg). Median half-life was 9.5 h (range 4.4-24.2 h). Median clearance was 0.02 L/h/kg (range 0.01-0.05 L/h/kg). Six hours after initial dose, eight children did not have recurrent seizure. One child had brief seizure at 20 min after initial dose. Seizure recurred in two children at 4th and 5th hour. Asymptomatic transient elevation of serum ammonia was observed in two children. Volume of distribution of 0.20 L/kg could be applied for initial intravenous administration with a favorable efficacy.
丙戊酸盐静脉给药在成人和儿童癫痫持续状态及系列性癫痫发作中的作用已有文献记载。药代动力学参数对于预测给药后的最佳治疗水平很有必要。2008年1月至12月在泰国儿童中开展了一项横断面研究，以确定静脉注射丙戊酸盐的药代动力学参数及安全性，供未来应用参考。共有11名年龄在1至15岁（平均年龄9.5岁）的儿童入组。以3mg/kg/分钟的速度静脉注射15 - 20mg/kg的丙戊酸盐，随后每6小时注射6mg/kg。在初始剂量前以及给药后半小时、1小时、2小时、4小时、5小时和6小时测定丙戊酸盐水平。在初始剂量前和6小时采集全血细胞计数、血清氨和肝功能测试结果。中位负荷剂量为19mg/kg（范围为15 - 20.5mg/kg）。输注后30分钟的中位最大浓度为98.8mcg/mL（范围为67 - 161mcg/mL）。中位分布容积为0.20L/kg（范围为0.15 - 0.53L/kg）。中位半衰期为9.5小时（范围为4.4 - 24.2小时）。中位清除率为0.02L/h/kg（范围为0.01 - 0.05L/h/kg）。初始剂量6小时后，8名儿童未出现癫痫复发。1名儿童在初始剂量后20分钟出现短暂癫痫发作。2名儿童在第4小时和第5小时癫痫复发。2名儿童观察到无症状的血清氨短暂升高。分布容积为0.20L/kg可用于初始静脉给药，疗效良好。
