title: Pharmacokinetics of orally administered melatonin in critically ill patients.
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.
authors.affiliation: Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Università degli Studi di Milano, Milano, Italy. giovanni.mistraletti@unimi.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Mistraletti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sabbatini
authors.forename: Martina
authors.initials: M
authors.lastname: Taverna
authors.forename: Maria Adele
authors.initials: MA
authors.lastname: Figini
authors.forename: Michele
authors.initials: M
authors.lastname: Umbrello
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
authors.forename: Elena
authors.initials: E
authors.lastname: Dozio
authors.forename: Roberto
authors.initials: R
authors.lastname: Esposti
authors.forename: Germana
authors.initials: G
authors.lastname: DeMartini
authors.forename: Franco
authors.initials: F
authors.lastname: Fraschini
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.forename: Gaetano
authors.initials: G
authors.lastname: Iapichino
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D002940:Circadian Rhythm; D016638:Critical Illness; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D006993:Hypnotics and Sedatives; D008550:Melatonin