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Pharmacokinetics of orally administered melatonin in critically ill patients


Critically ill patients exhibit reduced melatonin secretion, both in nocturnal peaks and basal daytime levels. Oral melatonin supplementation may be useful for known sedative and antioxidant properties.


Melatonin early enteral absorption and daily pharmacokinetics were determined in two cohorts of six high-risk patients in this prospective trial. During their third and fourth ICU day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immunoassay. Cohort 1: samples taken at 20:00, 20:45, 21:30, 24:00, 03:00, 06:00, 14:00, 20:00 to describe the daily pharmacokinetics. Cohort 2: 20:00, 20:05, 20:10, 20:20, 20:30, 20:45 to study the early absorption. On ICU day 3, endogenous levels were measured, while the absorption of exogenous melatonin was determined on ICU day 4 after administration, at 20:00, of 3 mg melatonin.


All basal levels were below the expected values. Following enteral administration, pharmacological levels were already reached in 5 minutes, with a serum peak after 16 minutes (half-absorption time: 3 minutes 17 seconds). The maximum serum level observed was 11,040 pg/ml and the disappearance rate indicated a half-elimination time of 1 hour 34 minutes. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hours following administration. No excessive sleepiness was reported in this patient group.


Critically ill patients exhibited reduced melatonin secretion, as reported in the literature. Despite the critical illness, the oral bioavailability was satisfactory: serum levels after oral administration showed basically unchanged intestinal absorption, while the disappearance rate was slower than reported elsewhere in healthy volunteers.

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Correspondence to B Moroni.

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Moroni, B., Mistraletti, G., Reiter, R. et al. Pharmacokinetics of orally administered melatonin in critically ill patients. Crit Care 14, P494 (2010).

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  • Melatonin
  • Critical Illness
  • Oral Bioavailability
  • Disappearance Rate
  • Maximum Serum