Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients

Bellapart, Judith, Roberts, Jason Alexander, Appadurai, Vinesh, Wallis, Steven C., Nunez-Nunez, Maria and Boots, Robert James (2016) Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients. Clinical Chemistry and Laboratory Medicine, 54 3: 467-472. doi:10.1515/cclm-2015-0323

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Author Bellapart, Judith
Roberts, Jason Alexander
Appadurai, Vinesh
Wallis, Steven C.
Nunez-Nunez, Maria
Boots, Robert James
Title Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
Journal name Clinical Chemistry and Laboratory Medicine   Check publisher's open access policy
ISSN 1437-4331
Publication date 2016-03
Year available 2015
Sub-type Article (original research)
DOI 10.1515/cclm-2015-0323
Open Access Status File (Publisher version)
Volume 54
Issue 3
Start page 467
End page 472
Total pages 6
Place of publication Berlin, Germany
Publisher Walter de Gruyter
Collection year 2016
Language eng
Formatted abstract
Background: Loss of circadian rhythms and reduced concentrations of endogenous melatonin are common in critically ill patients. After exogenous administration, supra-physiological concentrations in serum are only ephemeral, which may explain the absence of significant therapeutic effect on sleep. The aim of this study is to describe the pharmacokinetics of enteral melatonin in critically ill patients administered in a novel regimen aiming to simulate endogenous release.
Methods: Thirteen patients in the recovery phase of critical illness were randomised to receive enteral melatonin or placebo. In the melatonin group, a total of 6 mg was administered as solution through their feeding tube, commencing with a 3 mg loading dose at 9 pm and six subsequent 0.5 mg doses hourly. The placebo was administered using a similar regimen. Serial blood samples were taken and measured using a validated chromatographic method. The concentration-time data for serum melatonin concentrations were described using non-linear mixed-effects modelling.
Results: The observed concentrations in the melatonin patients were significantly higher than that observed in the placebo patients. The concentrations in the patients administered melatonin were also higher than endogenous melatonin concentrations previously reported in non-critically ill patients. The patients administered melatonin had a mean clearance, volume of distribution and absorption rate constant of melatonin was 55.2 L/h, 767 L and 0.76 h–1, respectively.
Conclusions: Exogenous administration of melatonin with a loading dose of 3 mg followed by an hourly dose of 0.5 mg demonstrates good oral bioavailability and results in supra-physiological and sustained concentrations of serum melatonin during 12 h overnight.
Keyword Critical illness
Drug delivery
Melatonin pharmacokinetics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online 1 September 2015

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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