title: Pharmacokinetics of melatonin in preterm infants.
abstract: OBJECTIVE
  Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials.
  
  
  METHODS
  Melatonin was administered to 18 preterm infants in doses ranging from 0.04-0.6 μg kg(-1) over 0.5-6 h. Pharmacokinetic profiles were analyzed individually and by population methods.
  
  
  RESULTS
  Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1 μg kg(-1)  h(-1) for 2 h showed a median half-life of 15.82 h and median maximum plasma concentration of 203.3 pg ml(-1) . On population pharmacokinetics, clearance was 0.045 l h(-1) , volume of distribution 1.098 l and elimination half-life 16.91 h with gender (P = 0.047) and race (P < 0.0001) as significant covariates.
  
  
  CONCLUSIONS
  A 2 h infusion of 0.1 μg kg(-1)  h(-1) increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants.
authors: Centre for the Developing Brain, King's College London, London, UK; Centre for the Developing Brain, Imperial College, London, UK; Division of Neonatology, Imperial College Healthcare NHS Trust, London, UK; Division of Neonatology, Guy's and St Thomas' NHS Trust, London, UK.
authors: Nazakat M
authors: NM
authors: Merchant
authors: Denis V
authors: DV
authors: Azzopardi
authors: Ahmed F
authors: AF
authors: Hawwa
authors: James C
authors: JC
authors: McElnay
authors: Benita
authors: B
authors: Middleton
authors: J
authors: J
authors: Arendt
authors: Tomoki
authors: T
authors: Arichi
authors: Pierre
authors: P
authors: Gressens
authors: A David
authors: AD
authors: Edwards
mesh_terms: D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D020249:Hormone Replacement Therapy / Q000379:methods*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012737:Sex Factors; D014018:Tissue Distribution
chemical_list: D008550:Melatonin
keywords: 6-sulfatoxymelatonin; melatonin; neuroprotective agents; pharmacokinetics; preterm infants