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Updated: May 13, 2026

Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption
Published on: July 30, 2016
Pharmacokinetics of melatonin in preterm infants
Nazakat M Merchant1, Denis V Azzopardi, Ahmed F Hawwa
1Centre 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.
Aims:
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 microg 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 microg 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 microg 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.
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