Dose assessment of melatonin in sepsis (DAMSEL2) study: Pharmacokinetics of two doses of oral melatonin in patients with sepsis

Helen Galley* (Corresponding Author), L. Allen, P.J. Collin, SP Galt , Nigel Robert Webster

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
4 Downloads (Pure)

Abstract

Sepsis is defined as a dysregulated host response to infection and high dose melatonin has been proposed as a treatment due to its antioxidant and anti-inflammatory properties. However, there are no data describing the pharmacokinetics of high dose oral melatonin in critically ill patients. We undertook an open label trial to determine tolerance of melatonin administration in these patients and pharmacokinetic analysis, to inform a planned randomised controlled trial. Two cohorts of critically ill patients with sepsis due to
community acquired pneumonia received either 20mg or 50mg oral melatonin liquid as a single dose. Blood samples and clinical measures were analysed over the next 24h. Melatonin was well tolerated and there were no adverse events. Pharmacokinetic modelling showed that a semi-physiological model, which incorporates saturable first-pass hepatic extraction, was a good fit for our data. Maximum levels of melatonin were extremely high in patients receiving the 50mg dose and levels of the major metabolite were much lower than expected and not different from those seen after 20mg, suggesting saturation at the
higher dose. We conclude that 20mg seems a suitable dose of the liquid melatonin in patients with sepsis.
Original languageEnglish
Article number12830
Number of pages12
JournalJournal of Pineal Research
Volume73
Issue number4
Early online date11 Sept 2022
DOIs
Publication statusPublished - 1 Nov 2022

Bibliographical note

Open Access via the Wiley OA Agreement
Funding
The work was funded by the Scottish Government under the Experimental and
Translational Medicine funding scheme of the Chief Scientist Office of Scotland, UK,
reference number ETM/538

Funding Information:
Written informed consent was obtained either from the patient, or, since most of the patients were not able to consent for themselves, their legal representative—a welfare guardian, a welfare attorney, a near relative or close friend, a clinical person not involved in the study, or another independent person nominated by the healthcare provider, according to the Medicines for Human Use (Clinical Trial) Regulations 2004. Trial Steering and Data and Safety Monitoring Committees with external chairs were established. The study was sponsored jointly by the University of Aberdeen and NHS Grampian and was monitored by NHS Grampian. The work was funded by the Chief Scientist Office of Scotland (Reference number ETM/538).

Funding Information:
The work was funded by the Scottish Government under the Experimental and Translational Medicine funding scheme of the Chief Scientist Office of Scotland, UK, reference number ETM/538.

Publisher Copyright:
© 2022 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd.

Keywords

  • melatonin
  • sepsis
  • pharmacokinetics
  • clinical trial

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