title: Pharmacokinetics of high-dose intravenous melatonin in humans.
abstract: This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Lars P H
authors.initials: LP
authors.lastname: Andersen
authors.affiliation: Multidisciplinary Pain Center 7612, Neuroscience Center, Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Mads U
authors.initials: MU
authors.lastname: Werner
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Mette M
authors.initials: MM
authors.lastname: Rosenkilde
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Andreas Q
authors.initials: AQ
authors.lastname: Fenger
authors.affiliation: Multidisciplinary Pain Center 7612, Neuroscience Center, Rigshospitalet, DK-2100 Copenhagen, Denmark.
authors.forename: Marian C
authors.initials: MC
authors.lastname: Petersen
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, DK-2730 Herlev, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Department of Surgery, Roskilde and K, ø, ge Hospital, University of Copenhagen, DK-4000 Roskilde, Denmark.
authors.forename: Ismail
authors.initials: I
authors.lastname: Gögenur
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D064368:Healthy Volunteers; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008550:Melatonin / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011930:Reaction Time / Q000187:drug effects; D055815:Young Adult
chemical_list: D008550:Melatonin
keywords: adverse effects; intravenous; melatonin; pharmacokinetics; sedation