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A mathematical model of diurnal variations in human plasma melatonin levelsStudies in animals and humans suggest that the diurnal pattern in plasma melatonin levels is due to the hormone's rates of synthesis, circulatory infusion and clearance, circadian control of synthesis onset and offset, environmental lighting conditions, and error in the melatonin immunoassay. A two-dimensional linear differential equation model of the hormone is formulated and is used to analyze plasma melatonin levels in 18 normal healthy male subjects during a constant routine. Recently developed Bayesian statistical procedures are used to incorporate correctly the magnitude of the immunoassay error into the analysis. The estimated parameters [median (range)] were clearance half-life of 23.67 (14.79-59.93) min, synthesis onset time of 2206 (1940-0029), synthesis offset time of 0621 (0246-0817), and maximum N-acetyltransferase activity of 7.17(2.34-17.93) pmol x l(-1) x min(-1). All were in good agreement with values from previous reports. The difference between synthesis offset time and the phase of the core temperature minimum was 1 h 15 min (-4 h 38 min-2 h 43 min). The correlation between synthesis onset and the dim light melatonin onset was 0.93. Our model provides a more physiologically plausible estimate of the melatonin synthesis onset time than that given by the dim light melatonin onset and the first reliable means of estimating the phase of synthesis offset. Our analysis shows that the circadian and pharmacokinetics parameters of melatonin can be reliably estimated from a single model.
Document ID
20040173012
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Brown, E. N.
(Massachusetts General Hospital, Harvard Medical School Boston 02114, United States)
Choe, Y.
Shanahan, T. L.
Czeisler, C. A.
Date Acquired
August 22, 2013
Publication Date
March 1, 1997
Publication Information
Publication: The American journal of physiology
Volume: 272
Issue: 3 Pt 1
ISSN: 0002-9513
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: 1-P01-AG 09975
CONTRACT_GRANT: 1-R01-GM-53559
CONTRACT_GRANT: 1-R01-AG-06072
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Number 70-10
NASA Discipline Number 18-10
NASA Discipline Regulatory Physiology
NASA Program Data Analysis
Non-NASA Center
NASA Program Space Physiology and Countermeasures

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