Kandrotas R J, Cranfield T L, Gal P, Ransom J L, Weaver R L
Greensboro Area Health Education Center, North Carolina.
Ther Drug Monit. 1990 Mar;12(2):139-43. doi: 10.1097/00007691-199003000-00005.
The effect of phenobarbital administration on theophylline clearance was studied in 24 premature neonates. Aminophylline was administered according to a standard protocol of 6 mg/kg loading dose followed by a maintenance dose of 2.5-5 mg/kg/12 h. Of the 24 neonates studied, 12 received a mean phenobarbital dose of 26.34 mg/kg/d (ranging from 2 mg every 24 h to 25 mg every 12 h) and the mean phenobarbital concentration was 56.12 micrograms/ml (range 22-112 micrograms/ml). The remaining 12 patients did not require phenobarbital therapy but did receive aminophylline alone. The two groups were closely matched for gestational age, 5-min Apgar scores, and sex (p greater than 0.2). Steady-state theophylline clearance was determined at least once a week for four or more separate weeks. The study lasted a minimum of 8 wk and if more than one theophylline clearance was determined in any given week, the mean of these clearances was used. Both groups demonstrated an increase in mean theophylline clearance over time (from 15.75 and 16.67 ml/h/kg to 30.33 and 35.42 ml/h/kg for the aminophylline and aminophylline plus phenobarbital groups, respectively). The mean slope, an indicator of the average change in theophylline clearance, was 2.19 for the aminophylline group and 3.27 for the aminophylline plus phenobarbital group (p greater than 0.2), indicating that the theophylline clearance for neonates receiving phenobarbital was not significantly different from that for neonates receiving aminophylline alone. Based on this information, aminophylline does not need to be adjusted solely based on concomitant phenobarbital administration; however, theophylline concentrations should be monitored since theophylline clearance can change rapidly and unpredictably in neonates.
在24例早产儿中研究了给予苯巴比妥对氨茶碱清除率的影响。氨茶碱按照6mg/kg负荷剂量的标准方案给药，随后是2.5 - 5mg/kg/12h的维持剂量。在研究的24例新生儿中，12例接受的苯巴比妥平均剂量为26.34mg/kg/d（范围为每24小时2mg至每12小时25mg），苯巴比妥平均浓度为56.12μg/ml（范围22 - 112μg/ml）。其余12例患者不需要苯巴比妥治疗，但仅接受氨茶碱治疗。两组在胎龄、5分钟阿氏评分和性别方面密切匹配（p>0.2）。在至少连续四周的时间里，每周至少测定一次稳态氨茶碱清除率。该研究至少持续8周，如果在任何给定周内测定了多个氨茶碱清除率，则使用这些清除率的平均值。两组均显示随着时间推移氨茶碱平均清除率增加（氨茶碱组和氨茶碱加苯巴比妥组分别从15.75和16.67ml/h/kg增加到30.33和35.42ml/h/kg）。平均斜率是氨茶碱清除率平均变化的一个指标，氨茶碱组为2.19，氨茶碱加苯巴比妥组为3.27（p>0.2），这表明接受苯巴比妥的新生儿的氨茶碱清除率与仅接受氨茶碱的新生儿相比无显著差异。基于此信息，氨茶碱不需要仅基于同时给予苯巴比妥而进行调整；然而，由于新生儿的氨茶碱清除率可能迅速且不可预测地变化，因此应监测氨茶碱浓度。
