Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants |
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Authors: | T Ahola V Fellman R Laaksonen J Laitila R Lapatto P J Neuvonen K O Raivio |
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Institution: | (1) Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, P.O. Box 281, FIN-00029 Helsinki, Finland e-mail: terhi.ahola@helsinki.fi Tel.: +358-9-47174777; Fax: +358-9-47174713, FI;(2) Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland, FI;(3) Institute of Biomedicine, University of Helsinki, Helsinki, Finland, FI |
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Abstract: | 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.
Received: 12 April 1999 / Accepted in revised form: 18 August 1999 |
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Keywords: | Antioxidant Free radicals Glutathione |
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