Simons F E, Rigatto H, Simons K J
Semin Perinatol. 1981 Oct;5(4):337-45.
Theophylline is a safe, effective drug for the treatment of apnea of prematurity. The pharmacokinetics of theophylline have been studied extensively in preterm neonates. There is some inter-infant variability, but generally, compared to children and adults, prolonged half-life values and low clearance rates have been found: the apparent volume of distribution is larger and protein binding of the drug is decreased. A unique pattern of metabolism involving methylation to caffeine has been identified. Theophylline maintenance dose requirements are much lower in neonates than in children. When therapy is begun, a useful guide is to give a loading dose of 5 mg/kg anhydrous theophylline followed by maintenance doses of 2 mg/kg every 12 hr. In many infants, this will suffice to prevent apnea without producing signs of toxicity. After commencement of therapy, doses must be individualized for each infant on the basis of serum theophylline concentration monitoring and monitoring for apnea. Evidence of theophylline toxicity in neonates may be subtle, and only scanty data are available regarding possible long-term effects of chronic theophylline treatment of neonates.
氨茶碱是治疗早产儿呼吸暂停的一种安全、有效的药物。氨茶碱的药代动力学已在早产新生儿中进行了广泛研究。婴儿之间存在一定的个体差异，但总体而言，与儿童和成人相比，已发现其半衰期延长、清除率较低：药物的表观分布容积较大且蛋白结合率降低。已确定一种独特的代谢模式，即通过甲基化生成咖啡因。新生儿氨茶碱维持剂量需求远低于儿童。开始治疗时，一个有用的指导是给予5mg/kg无水氨茶碱的负荷剂量，随后每12小时给予2mg/kg的维持剂量。在许多婴儿中，这足以预防呼吸暂停而不产生毒性迹象。治疗开始后，必须根据血清氨茶碱浓度监测和呼吸暂停监测为每个婴儿个体化调整剂量。新生儿氨茶碱毒性的证据可能很细微，关于氨茶碱长期治疗新生儿可能产生的长期影响，仅有少量数据。
