Gilman J T, Gal P, Levine R S, Hersh C B, Erkan N V
Ther Drug Monit. 1986;8(1):4-10. doi: 10.1097/00007691-198603000-00002.
The pharmacokinetics of intravenous theophylline were prospectively studied in 179 premature babies. Interrelated variables were analyzed for their influence on theophylline serum clearance. Gestational age, gender, duration of treatment, body weight, and Apgar scores were not found to correlate significantly with theophylline clearance. Weak but statistically significant correlations were found between serum clearance and postnatal (p less than 0.005) and postconceptional age (p less than 0.01). No significant difference in mean serum clearance (Cls) values was found between small-for-gestational-age (SGA) patients (Cls = 17.9 +/- 5.3 ml/kg/h) and appropriate-for-gestational-age (AGA) patients (Cls = 18.8 +/- 5.8 ml/kg/h). Conversely, asphyxiated patients had significantly lower mean clearance values than nonasphyxiated patients (16.4 +/- 5.3 ml/kg/h vs. 20.2 +/- 5.4 ml/kg/h, respectively, p less than 0.001). Volume of distribution for theophylline (n = 147) was 0.77 +/- 0.17 L/kg; there was no significant difference in distribution volumes between asphyxiated and nonasphyxiated patients or between SGA and AGA patients. Step-wise multiple regression analysis revealed postnatal age as the most important determinant of theophylline clearance among the variables analyzed (p less than 0.01). Postconceptional age had a statistically significant association with theophylline clearance in the entire group (n = 179, p less than 0.05). Duration of treatment had a small and statistically borderline effect (p less than 0.10) on theophylline clearance among nonasphyxiated infants when age factors were considered. Analysis of covariance confirmed the statistical effects of both postnatal age and asphyxia on theophylline serum clearance.
对179名早产儿进行了静脉注射氨茶碱的药代动力学前瞻性研究。分析了相关变量对氨茶碱血清清除率的影响。未发现胎龄、性别、治疗持续时间、体重和阿氏评分与氨茶碱清除率有显著相关性。血清清除率与出生后（p<0.005）和孕龄（p<0.01）之间存在弱但具有统计学意义的相关性。小于胎龄（SGA）患者（Cls = 17.9±5.3 ml/kg/h）与适于胎龄（AGA）患者（Cls = 18.8±5.8 ml/kg/h）的平均血清清除率（Cls）值无显著差异。相反，窒息患者的平均清除率值显著低于未窒息患者（分别为16.4±5.3 ml/kg/h和20.2±5.4 ml/kg/h，p<0.001）。氨茶碱的分布容积（n = 147）为0.77±0.17 L/kg；窒息患者与未窒息患者之间或SGA患者与AGA患者之间的分布容积无显著差异。逐步多元回归分析显示，在分析的变量中，出生后年龄是氨茶碱清除率的最重要决定因素（p<0.01）。孕龄与整个组（n = 179，p<0.05）的氨茶碱清除率有统计学意义的关联。在考虑年龄因素时，治疗持续时间对未窒息婴儿的氨茶碱清除率有较小且在统计学上接近临界的影响（p<0.10）。协方差分析证实了出生后年龄和窒息对氨茶碱血清清除率的统计学影响。
