Pharmacokinetics of Orally Administered Melatonin in Critically Ill Patients
Giovanni Mistraletti, Giovanni Sabbatini, Martina Taverna, Maria Adele Figini, Michele Umbrello, Paolo Magni, Massimiliano Ruscica, Elena Dozio, Roberto Esposti, Germana DeMartini, Franco Fraschini, Rita Rezzani, Russel J. Reiter, and Gaetano Iapichino
J. Pineal Res. 2010; 48
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 radioimmuno-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.
A new frontier in critical care: saving the injuried brain.
Gestire il doloreFlowchart dolore
Gestire la sedazioneFlowchart sedaz/agitaz
Gestire il deliriumFlowchart Delirium
Scheda di lavoro CAM-ICU
Questo sito è stato realizzato grazie al contributo di:
Finanziamento per la Ricerca Indipendente
(Decreto DGS 13456 del 22 dicembre 2010)