title: Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants.
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.
authors.affiliation: Hospital for Children and Adolescents, Helsinki University Central Hospital, University of Helsinki, Finland. terhi.ahola@helsinki.fi
authors.forename: T
authors.initials: T
authors.lastname: Ahola
authors.forename: V
authors.initials: V
authors.lastname: Fellman
authors.forename: R
authors.initials: R
authors.lastname: Laaksonen
authors.forename: J
authors.initials: J
authors.lastname: Laitila
authors.forename: R
authors.initials: R
authors.lastname: Lapatto
authors.forename: P J
authors.initials: PJ
authors.lastname: Neuvonen
authors.forename: K O
authors.initials: KO
authors.lastname: Raivio
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000367:Age Factors; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003545:Cysteine / Q000097:blood; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D003545:Cysteine; D000111:Acetylcysteine