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

Clinical Chemistry and Laboratory Medicine : CCLM
Judith BellapartRobert James Boots

Abstract

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. 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. 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 ...Continue Reading

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Citations

Apr 4, 2017·International Journal of Molecular Sciences·Giovanni MistralettiGaetano Iapichino
May 11, 2018·The Cochrane Database of Systematic Reviews·Sharon R LewisAndrew F Smith
Mar 24, 2016·Clinical Pharmacokinetics·Lars Peter Holst AndersenRussel J Reiter
May 6, 2019·Clinical Drug Investigation·Mahshid Yeganeh SalehpourMohammad Hosein Farzaei
Sep 13, 2019·Journal of Intensive Care Medicine·Elena DiazSilvia Pérez
Apr 14, 2020·Diabetology & Metabolic Syndrome·Mohammad Hossein PourhanifehSaeed Mehrzadi
Apr 21, 2019·Clinical Endocrinology·Giovanni MistralettiGaetano Iapichino
Apr 16, 2021·Minerva anestesiologica·Rob J BootsChristopher Zappala

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Methods Mentioned

BETA
sedation

Software Mentioned

Wings
NONMEM

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