Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants
Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants
复制标题
DOI：
10.1007/s002280050687
复制
发表时间：
1999-11-01
影响因子：
2.9
通讯作者：
Raivio, KO
中科院分区：
文献类型：
--
作者：
Ahola, T;Fellman, V;Raivio, KO
背景：活性氧被认为在早产儿的几种临床并发症中发挥作用。本研究的目的是确定早产儿静脉注射N-乙酰半胱氨酸的药代动力学。需要这些信息来评估N-乙酰半胱氨酸作为抗氧化剂在该患者组中的使用。10例患者静脉输注N-乙酰半胱氨酸（胎龄24.9-31.0周，体重500-1384 g）24小时（3.4-4.6 mg/kg/h），从出生后2.0-11.2 h开始（研究I），6例患者（胎龄25.9-29.7周，体重520-1335 g）持续6天（0.3-1.3 mg/kg/h），从24 h龄开始（研究II）。动脉血浆N-乙酰半胱氨酸和胱氨酸浓度测定从定时采样期间（研究I和II）和后（研究I）的N-乙酰半胱氨酸infrations.Results：在研究I中，N-乙酰半胱氨酸的平均消除半衰期为11小时（范围7.8-15.2小时）。N-乙酰半胱氨酸的平均血浆清除率为37 ml/kg/h（范围13-62 ml/kg/h），平均分布容积为573 ml/kg（范围167-1010 ml/kg）。血浆清除率和分布容积与体重（r = 0.81，P < 0.01; r = 0.78，P <0.01）和胎龄（r = 0.71，P < 0.05; r = 0.64，P < 0.05）相关。在研究II中，稳态浓度的N-乙酰半胱氨酸在2-3天内达到5个6例患者在一个恒定的infusing.Conclusions：N-乙酰半胱氨酸在早产儿的药代动力学显着依赖于体重和胎龄。N-乙酰半胱氨酸的消除在早产新生儿中比在成人中慢得多。
Background: Reactive oxygen species have been considered to play a role in several clinical complications in pre-term infants. The aim of this study was to determine the pharmacokinetics of intravenous N-acetylcysteine in pre-term neonates. This information is needed to evaluate the use of N-acetylcysteine as an antioxidant in this patient group.Methods: N-acetylcysteine was infused intravenously in ten patients (gestational age 24.9-31.0 weeks, weight 500-1384 g) for 24 h (3.4-4.6 mg/kg/h), starting 2.0-11.2 h from birth (study I) and in six patients (gestational age 25.9-29.7 weeks, weight 520-1335 g) for 6 days (0.3-1.3 mg/kg/h), starting at the age of 24 h (study II). Arterial plasma N-acetylcysteine and cyst(e)ine concentrations were determined from timed samples taken during (study I and II) and after (study I) the N-acetylcysteine infusion.Results: In study I, the mean elimination half-life of N-acetylcysteine was 11 h (range 7.8-15.2 h). The mean plasma clearance of N-acetylcysteine was 37 ml/kg/h (range 13-62 ml/kg/h) and the mean volume of distribution was 573 ml/kg (range 167-1010 ml/kg). The plasma clearance and volume of distribution correlated with weight (r = 0.81, P < 0.01, and r = 0.78, P < 0.01, respectively) and with gestational age (r = 0.71, P < 0.05, and r = 0.64, P < 0.05, respectively). In study II, the steady-state concentration of N-acetylcysteine was reached in 2-3 days in five of six patients during a constant infusion.Conclusions: The pharmacokinetics of N-acetylcysteine in pre-term infants depend markedly on weight and gestational age. The elimination of N-acetylcysteine is much slower in pre-term new-borns than in adults.