Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
-
Judith Bellapart
,
Jason Alexander Roberts
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.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This work was supported by the Royal Brisbane and Women’s Hospital, Research Foundation project grant 2011. Jason Roberts is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1048652).
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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- Editorial
- The way of prostate cancer diagnostics
- Review
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- Opinion Paper
- The side effects of translational omics: overtesting, overdiagnosis, overtreatment
- Genetics and Molecular Diagnostics
- Rapid detection of non-deletional mutations causing α-thalassemia by multicolor melting curve analysis
- General Clinical Chemistry and Laboratory Medicine
- Patient pools and the use of “patient means” are valuable tools in quality control illustrated by a bone-specific alkaline phosphatase assay
- Long-term stability of glucose: 96-h study using Terumo Glycaemia tubes
- Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes
- Croatian laboratories have a good knowledge of the proper detection and management of hemolyzed, icteric and lipemic samples
- Fetal exposure to ethanol: relationship between ethyl glucuronide in maternal hair during pregnancy and ethyl glucuronide in neonatal meconium
- Comparing the effect of isotopically labeled or structural analog internal standards on the performance of a LC-MS/MS method to determine ciclosporin A, everolimus, sirolimus and tacrolimus in whole blood
- Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study
- Comparison of functional fibrinogen (FF/CFF) and FIBTEM in surgical patients – a retrospective study
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- Assessment of serum free light chain levels in healthy adults immediately after marathon running
- Pharmacokinetics of a novel dosing regimen of oral melatonin in critically ill patients
- Cancer Diagnostics
- An epidemiology-based model as a tool to monitor the outbreak of inappropriateness in tumor marker requests: a national scale study
- Comparative analysis of prostate cancer specific biomarkers PCA3 and ERG in whole urine, urinary sediments and exosomes
- Infectious Diseases
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- Between analyser differences in chloride measurements and thus anion gap cause different interpretations of the acid-base balance
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