Year: 2013
Type: dissertation
Study design: Clinical Trial
Abstract: Background and purpose: Advances in perinatal care have increased survival rates of \ninfants but long-term neurodisability and social consequences have remained \nunchanged over the last decade. Preterm infants are deprived of the normal \nintrauterine exposure to maternal melatonin and experimental studies suggest that \nmelatonin has a neuroprotective effect on cerebral white matter injury. However, \npharmacokinetic data on melatonin in preterm infants are lacking, which hinders \npotential therapeutic trials. The aims of this study were to determine the \npharmacokinetics of melatonin in the relevant preterm population, assess the \ntolerability of melatonin and determine a dose regime that would allow replication of \nadult melatonin levels. \nMethods: In a multi-centre, single dose escalation/de-escalation, open label study in \npreterm infants less than 31 weeks gestation, melatonin was administered to \neighteen infants in doses ranging from 0.04-0.6 micrograms/kilograms, over 0.5-6 \nhours. Pharmacokinetic profiles were analysed individually and by population \nmethods. \nResults: Baseline melatonin was largely undetectable. At the highest and lowest \ndoses half-life could not be calculated due to blood concentrations not reaching a \nconsistent steady state, but infants receiving melatonin at 0.1 \nmicrograms/kilogram/hour for 2 hours showed a median half-life of 15.82 hours and \nmedian maximum plasma concentration of 203.3 picograms/millilitre. Population \npharmacokinetic analysis showed that clearance was 0.045 litre/hour, volume of distribution 1.098 litres and elimination half-life 16.91 hours with gender (p=0.047) \nand race (p<0.0001) as significant covariates. Melatonin infusion appeared to be well \ntolerated in preterm infants. \nConclusions: The pharmacokinetic profile of melatonin in preterm infants differs from \nthat of adults. Slow clearance makes replication of adult and thus fetal concentrations \nof melatonin problematic. Further studies are needed to confirm these findings.
Source: Spiral (Imperial College London)
Author: Nazakat Merchant
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3012395838