Whelan H T, Hendeles L, Haberkern C M, Neims A H
Neurology. 1983 Jan;33(1):106-8. doi: 10.1212/wnl.33.1.106.
A term neonate was being treated with intravenous phenytoin. To maintain a serum level above 10 micrograms per milliliter and abolish seizure activity, it was necessary to carry out repeated serum concentration measurements, administer several loading doses, and administer an unusually large maintenance dose (25 mg per kilogram per day), divided into a short dosing interval (6 hours). Declining serum levels from postnatal days 8 to 13 on a constant dose of 9 mg per kilogram per day suggested that the rate of phenytoin metabolism was gradually increasing; rapid elimination was documented on day 18 by a half-life measurement of 8.8 hours from three samples. The changing pharmacokinetics were attributed to maturation of oxidative metabolism of phenytoin, concurrent phenobarbital administration, or both. The need for additional loading doses and maintenance dose increases must be guided by serum concentration measurements to obtain maximum benefit with minimal risk of toxicity.
一名足月新生儿正在接受静脉注射苯妥英治疗。为了将血清水平维持在每毫升10微克以上并消除癫痫发作活动，有必要进行反复的血清浓度测量，给予多次负荷剂量，并给予异常大的维持剂量（每天每公斤25毫克），分为短给药间隔（6小时）。在每天每公斤9毫克的恒定剂量下，出生后第8天至第13天血清水平下降，这表明苯妥英的代谢率逐渐增加；在第18天，通过对三个样本进行半衰期测量，记录到消除迅速，半衰期为8.8小时。药代动力学的变化归因于苯妥英氧化代谢的成熟、同时给予苯巴比妥或两者兼而有之。额外负荷剂量和维持剂量增加的必要性必须以血清浓度测量为指导，以获得最大益处并将毒性风险降至最低。
