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*

*Corresponding author for this work

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 0.04-0.6μgkg-1 over 0.5-6h. Pharmacokinetic profiles were analyzed individually and by population methods. Results: Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1μgkg-1h-1 for 2h showed a median half-life of 15.82h and median maximum plasma concentration of 203.3pgml-1. On population pharmacokinetics, clearance was 0.045lh-1, volume of distribution 1.098l and elimination half-life 16.91h with gender (P = 0.047) and race (P < 0.0001) as significant covariates. Conclusions: A 2h infusion of 0.1μgkg-1h-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

Keywords

  • 6-sulfatoxymelatonin
  • Melatonin
  • Neuroprotective agents
  • Pharmacokinetics
  • Preterm infants

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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    Merchant, N. M., Azzopardi, D. V., Hawwa, A. F., Mcelnay, J. C., Middleton, B., Arendt, J., Arichi, T., Gressens, P., & Edwards, A. D. (2013). Pharmacokinetics of melatonin in preterm infants. British Journal of Clinical Pharmacology, 76(5), 725-733. https://doi.org/10.1111/bcp.12092