Nahata M C, Masuoka T, Edwards R C
College of Pharmacy, Ohio State University, Columbus 43210.
J Perinatol. 1988 Fall;8(4):318-20.
Although phenobarbital is the most widely used drug to control seizures, dosage guidelines are not available for infants of varying gestational ages. The primary objective of this study was to develop age specific dosage guidelines for phenobarbital in newborn infants with seizures. Fifty-one patients (27 premature infants, gestational ages 27 to 38 weeks; 24 term infants) receiving phenobarbital, 3 to 6 mg/kg/d were studied during the first month of life. Multiple serum concentrations were determined in each patient during extended therapy. Trough serum concentration of phenobarbital ranged from 12.5 to 50.2 mcg/mL. Phenobarbital serum concentrations were within therapeutic range (15 to 40 mcg/mL) in 99 of 114 measurements at a maintenance dose of 3.5 to 4.5 mg/kg/d. The remaining 15 measurements were made in infants, greater than 35 weeks' gestation and required phenobarbital doses of 4.0 to 5.0 mg/kg/d to achieve therapeutic serum concentration. These data suggest that the initial maintenance dose of phenobarbital during the first month of life should be 3.5 to 4.5 mg/kg/d in infants less than or equal to 35 weeks and 4.0 to 5.0 mg/kg/d in those greater than 35 weeks' gestation. Term infants with asphyxia had higher trough serum concentration than those without asphyxia (P less than 0.005). In nine infants, trough serum concentration normalized for dose decreased substantially during a 3-weeks period (P less than 0.0005). This suggests that phenobarbital serum concentration should be monitored frequently during the first month of life.
尽管苯巴比妥是控制癫痫发作最广泛使用的药物，但针对不同胎龄的婴儿尚无剂量指南。本研究的主要目的是制定新生儿癫痫患者苯巴比妥的年龄特异性剂量指南。对51例接受苯巴比妥治疗（3至6mg/kg/d）的患者（27例早产儿，胎龄27至38周；24例足月儿）在出生后的第一个月进行了研究。在延长治疗期间测定了每位患者的多个血清浓度。苯巴比妥的谷血清浓度范围为12.5至50.2mcg/mL。在维持剂量为3.5至4.5mg/kg/d时，114次测量中有99次苯巴比妥血清浓度在治疗范围内（15至40mcg/mL）。其余15次测量是在胎龄大于35周的婴儿中进行的，这些婴儿需要4.0至5.0mg/kg/d的苯巴比妥剂量才能达到治疗性血清浓度。这些数据表明，出生后第一个月内，胎龄小于或等于35周的婴儿苯巴比妥的初始维持剂量应为3.5至4.5mg/kg/d，胎龄大于35周的婴儿应为4.0至5.0mg/kg/d。窒息足月儿的谷血清浓度高于无窒息者（P<0.005）。在9例婴儿中，剂量标准化后的谷血清浓度在3周内大幅下降（P<0.0005）。这表明在出生后的第一个月应频繁监测苯巴比妥血清浓度。
