Pharmacokinetics of melatonin in preterm infants

Nazakat M. Merchant, Denis V. Azzopardi, Ahmed F. Hawwa, James C. McElnay, Benita Middleton, J. Arendt, Tomoki Arichi, Pierre Gressens, A. David Edwards

Research output: Contribution to journalArticlepeer-review

Abstract

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 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.
Original languageEnglish
Pages (from-to)725-733
Number of pages9
JournalBritish Journal of Clinical Pharmacology
Volume76
Issue number5
DOIs
Publication statusPublished - Nov 2013

Bibliographical note

© 2013 King's College, London. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Keywords

  • 6-sulfatoxymelatonin
  • melatonin
  • neuroprotective agents
  • pharmacokinetics
  • preterm infants

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