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. Its 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 Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. 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 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr 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 disappearance rate was slower than reported elsewhere in healthy volunteers.

Pharmacokinetics of orally administered melatonin in critically ill patients / G. Mistraletti, G. Sabbatini, M. Taverna, M.A. Figini, M. Umbrello, P. Magni, M. Ruscica, E. Dozio, R. Esposti, G. Demartini, F. Fraschini, R. Rezzani, R.J. Reiter, G. Iapichino. - In: JOURNAL OF PINEAL RESEARCH. - ISSN 0742-3098. - 48:2(2010 Mar), pp. 142-147. [10.1111/j.1600-079X.2009.00737.x]

Pharmacokinetics of orally administered melatonin in critically ill patients

G. Mistraletti
;
G. Sabbatini
Secondo
;
M. Taverna;M.A. Figini;M. Umbrello;P. Magni;M. Ruscica;E. Dozio;R. Esposti;G. Demartini;F. Fraschini;G. Iapichino
Ultimo
2010-03

Abstract

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. Its 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 Intensive Care Unit (ICU) day, they underwent two different sets of repeated blood samples to detect serum melatonin levels through radio-immuno-assay. 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 min, with a serum peak after 16 min (half-absorption time: 3 min 17 s). The maximum serum level observed was 11040 pg/mL and the disappearance rate indicated a half-elimination time of 1 hr 34 min. Serum melatonin levels decreased significantly after midnight; pharmacological levels were maintained up to 10 hr 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 disappearance rate was slower than reported elsewhere in healthy volunteers.
critically ill; enteral absorption; intensive care; melatonin; oral bioavailability; pharmacokinetics; radio-immuno-assay; administration, oral; aged; aged, 80 and over; biological availability; circadian rhythm; female; humans; hypnotics and sedatives; male; melatonin; middle aged; prospective studies; critical illness; endocrinology
Settore MED/41 - Anestesiologia
Settore MED/05 - Patologia Clinica
Settore BIO/14 - Farmacologia
Settore BIO/09 - Fisiologia
Settore MED/04 - Patologia Generale
Settore MED/13 - Endocrinologia
gen-2010
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/241539
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