Kandrotas R J, Gal P, Hansen C J, Ransom J L, Weaver R L
Moses H. Cone Memorial Hospital, Greensboro, North Carolina.
Ther Drug Monit. 1988;10(4):390-4. doi: 10.1097/00007691-198804000-00004.
The effect of total parenteral nutrition (TPN) induced cholestasis on theophylline clearance was examined in premature neonates. Thirty-six neonates receiving TPN and theophylline concurrently were reviewed. 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 every 12 h. Of the 36 neonates reviewed, 18 developed cholestasis (direct bilirubin greater than or equal to 1 mg/100 ml and direct bilirubin greater than or equal to 60% of total bilirubin). The remaining 18 did not develop cholestasis. The two groups were closely matched for gestational age, 5-min apgar score, and sex. The neonates with cholestasis had a mean maximum direct bilirubin of 5.19 mg/100 ml (range 1-13.8 mg/100 ml) as compared to the patients without cholestasis who had a mean maximum direct bilirubin of 0.54 mg/100 ml (range 0.3-0.8 mg/100 ml). Steady-state theophylline clearance was determined at least once a week for at least 4 separate weeks. The study lasted a minimum of 8 weeks, and if more than one theophylline clearance was determined in any given week, the mean of these clearances was used. Both groups demonstrated a significant increase in mean theophylline clearance over time (from 16.09 and 18.60 ml/h/kg to 28.65 and 24.73 ml/h/kg for the cholestatic and noncholestatic groups, respectively). The mean slope, an indicator of the average rate of change of theophylline clearance, was 1.4 for the noncholestatic group and 2.5 for the cholestatic group, indicating that the theophylline clearance for neonates with cholestasis was not significantly different from that for neonates with normal liver function (p = 0.61) over time.
在早产儿中研究了全胃肠外营养（TPN）诱导的胆汁淤积对茶碱清除率的影响。回顾了36例同时接受TPN和茶碱治疗的新生儿。氨茶碱按照6mg/kg负荷剂量的标准方案给药，随后每12小时给予2.5 - 5mg/kg的维持剂量。在回顾的36例新生儿中，18例发生了胆汁淤积（直接胆红素大于或等于1mg/100ml且直接胆红素大于或等于总胆红素的60%）。其余18例未发生胆汁淤积。两组在胎龄、5分钟阿氏评分和性别方面密切匹配。发生胆汁淤积的新生儿平均最大直接胆红素为5.19mg/100ml（范围1 - 13.8mg/100ml），而未发生胆汁淤积的患儿平均最大直接胆红素为0.54mg/100ml（范围0.3 - 0.8mg/100ml）。至少连续4周每周至少测定一次稳态茶碱清除率。研究持续至少8周，如果在任何给定周内测定了多个茶碱清除率，则使用这些清除率的平均值。两组均显示随着时间推移平均茶碱清除率显著增加（胆汁淤积组和非胆汁淤积组分别从16.09和18.60ml/h/kg增加到28.65和24.73ml/h/kg）。平均斜率是茶碱清除率平均变化率的一个指标，非胆汁淤积组为1.4，胆汁淤积组为2.5，表明随着时间推移，胆汁淤积新生儿的茶碱清除率与肝功能正常的新生儿相比无显著差异（p = 0.61）。
