Abstract
Background and purpose
Preterm infants are deprived of the normal intrauterine 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 eighteen preterm infants in doses ranging from 0.04-0.6 micrograms/kilograms, over 0.5-6 hours. Pharmacokinetic profiles were analysed individually and by population methods.
Results
Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1 micrograms/kilogram/hour for 2 hours showed a median half-life of 15.82 hours and median maximum plasma concentration of 203.3 picograms/millilitre. On population pharmacokinetics, clearance was 0.045 litre/hour, volume of distribution 1.098 litres and elimination half-life 16.91 hours with gender (p=0.047) and race (p<0.0001) as significant covariates.
Conclusions
A two-hour infusion of 0.1 micrograms/kilogram/hour 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 used to guide therapeutic clinical trials of melatonin in preterm infants.
Preterm infants are deprived of the normal intrauterine 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 eighteen preterm infants in doses ranging from 0.04-0.6 micrograms/kilograms, over 0.5-6 hours. Pharmacokinetic profiles were analysed individually and by population methods.
Results
Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1 micrograms/kilogram/hour for 2 hours showed a median half-life of 15.82 hours and median maximum plasma concentration of 203.3 picograms/millilitre. On population pharmacokinetics, clearance was 0.045 litre/hour, volume of distribution 1.098 litres and elimination half-life 16.91 hours with gender (p=0.047) and race (p<0.0001) as significant covariates.
Conclusions
A two-hour infusion of 0.1 micrograms/kilogram/hour 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 used to guide therapeutic clinical trials of melatonin in preterm infants.
| Original language | English |
|---|---|
| Journal | British Journal of Clinical Pharmacology |
| DOIs | |
| Publication status | E-pub ahead of print - 21 Feb 2013 |