The Absolute Bioavailability of Oral Melatonin

DeMuro, Rob L.; Nafziger, Anne N.; Blask, David E.; Menhinick, Anne M.; Bertino, Joseph S.

doi:10.1177/00912700022009422

Cited by 224 publications

(203 citation statements)

References 14 publications

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“…At a low dose, which does not generate a long presence of enhanced melatonin in the blood, no phase shift will occur at DLMO because of the silent zone, although the dose would suffice for synchronizing when given in the delay or the advance part of the PRC. As mentioned, commercial pills can generate strong, supraphysiological levels of circulating melatonin [24]. If the doses are high enough, melatonin may spill over from the silent zone into the delay part of the PRC.…”

Section: Consequences Of the Phase Response Curvementioning

confidence: 99%

“…The time course of exogenous, orally applied melatonin or other melatonergic drugs may not sufficiently mimic the natural, endogenous pattern in the blood. Especially, the primary Sleep Vigilance rise of melatonin after intake can strongly exceed, dosedependently by one or more orders of magnitude, the levels that are physiologically attained in the first hours of night [24]. However, the interindividual variation in the pharmacokinetics of exogenous melatonin is remarkably high [25].…”

Section: Different Requirements For Sleep Onset and Sleep Maintenancementioning

confidence: 99%

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Melatonergic Sleep Promotion: Fundamental Chronobiological Issues Concerning Sleep Onset and Maintenance, Dose and Duration of Action

Hardeland

2017

Sleep Vigilance

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Purpose This review summarizes the conditions under which sleep promotion by melatonin or other melatonergic drugs can be successfully achieved or not. Importantly, the chronobiological rules are outlined which have to be followed in cases in which an etiology of circadian deviations is responsible for sleep difficulties. Dose and Duration of Action Sleep initiation is already possible with low doses (below 1 mg) of immediate-release melatonin. Prolonged actions have only caused moderate improvements of sleep maintenance. At elevated doses, melatonin may occasionally cause sleep fragmentation in some patients. Low doses (below 1 mg) of short-acting melatonin are also suitable for entraining and readjusting circadian rhythms, because circadian oscillators are particularly sensitive to nonparametric synchronizing signals. Phase Response Curve Successful entrainment of circadian rhythms is only possible if the phase response curve (PRC) is considered, which consists of phases of a silent zone with poor resetting, a delay and an advance part. Notably, the dim light melatonin onset (DLMO) is still in the silent zone. Conclusions For purposes of melatonergic treatment, the knowledge of synchronization-sensitive phases within the circadian cycle is helpful in correcting circadian rhythm sleep disorders, otherwise poorly entrainable rhythms, e.g., in blind people, and mood disorders with circadian etiology. The disregard of the PRC leads to false conclusions on inefficacy of melatonin or other melatonergic drugs. Correcting actions by melatonin should not be inhibited by other drugs. For instance, attempts of shortening a circadian oscillation by well-timed melatonin should not be counteracted by period-lengthening drugs, such as lithium.

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Section: Consequences Of the Phase Response Curvementioning

confidence: 99%

Section: Different Requirements For Sleep Onset and Sleep Maintenancementioning

confidence: 99%

Melatonergic Sleep Promotion: Fundamental Chronobiological Issues Concerning Sleep Onset and Maintenance, Dose and Duration of Action

Hardeland

2017

Sleep Vigilance

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“…86 To mimic the physiologically nocturnal secretion, extended release preparations of melatonin are available in the market mainly for the management of insomnia. Melatonin is metabolized by CYP1A2 and CYP2C19 in the liver and excreted via renal after glucuronate and sulfate conjugation.…”

Section: Melatoninmentioning

confidence: 99%

Management of Late-Life Insomnia

Yang

Lee²,

Yeh

2011

Clinical Medicine Insights: Geriatrics

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Insomnia is a common complaint that can have significant daytime consequences. The prevalence of chronic insomnia may increase with age. The management of late-life insomnia can be complicated because aging is associated with normal changes in sleep structure, continuity, and timing, as well as a higher rate of medical and psychiatric disorders. A thorough evaluation and conceptualization of patients' problems should be conducted for effective treatment planning. Both non-pharmacological and pharmacological strategies have been proven effective in treating insomnia in elderly populations. Behavioral intervention and cognitive behavioral therapy for insomnia are recommended as first considerations. Light therapy may be administered for misalignment of the circadian phase. When necessary, hypnotic medications may be added with adequate safety precautions and consideration of comorbid conditions.

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“…For clinical purposes (mainly disorders of the sleep-wake cycle and insomnia in the elderly), exogenous MT administration should mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favorable due to its short half-life of elimination (DeMuro, Nafziger, Blask, Menhinick, & Bertino, 2000;Mallo et al, 1990). The pharmacokinetics of MT-SLN has been examined in humans after administration by oral and transdermal route (Priano et al, 2007) In vitro, MT-SLN produced a flux of MT of 1 mg/h/cm 2 through hairless mice skin, following a pseudo-zero-order kinetics (45)…”

Section: Drug-loaded Solid Lipid Nanoparticlesmentioning

confidence: 99%

Solid lipid nanoparticles and microemulsions for drug delivery

Gasco¹,

Priano

Zara

2009

Nanoneuroscience and Nanoneuropharmacology

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Abstract:The chapter examined solid lipid nanoparticles (SLN) and microemulsions, chosen as carriers of drugs, administered in vivo to be transported to the central nervous system. Drugs of different structures and for different therapies have been studied such as doxorubicin SLN stealth and nonstealth administered in rats by intravenous route, apomorphine SLN administered in rats by duodenal route, melatonin SLN administered by transdermal and oral routes in humans, and apomorphine microemulsion administered by transdermal route in Parkinson's patients. The pharmacokinetics of the drug, followed in most studies, put in evidence that the many important pharmacokinetic parameters were notably improved versus the drug alone or in a commercial formulation.

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The Absolute Bioavailability of Oral Melatonin

Cited by 224 publications

References 14 publications

Melatonergic Sleep Promotion: Fundamental Chronobiological Issues Concerning Sleep Onset and Maintenance, Dose and Duration of Action

Melatonergic Sleep Promotion: Fundamental Chronobiological Issues Concerning Sleep Onset and Maintenance, Dose and Duration of Action

Management of Late-Life Insomnia

Solid lipid nanoparticles and microemulsions for drug delivery

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