title: Pharmacokinetics of oral and intravenous melatonin in healthy volunteers.
abstract: BACKGROUND
  The aim was to investigate the pharmacokinetics of oral and iv melatonin in healthy volunteers.
  
  
  METHODS
  The study was performed as a cohort crossover study. The volunteers received either 10 mg oral melatonin or 10 mg intravenous melatonin on two separate study days. Blood samples were collected at different time points following oral administration and short iv infusion, respectively. Plasma melatonin concentrations were determined by RIA technique. Pharmacokinetic analyses were performed by "the method of residuals" and compartmental analysis. The pharmacokinetic variables: k a, t 1/2 absorption, t max, C max, t 1/2 elimination, AUC 0-∞, and bioavailability were determined for oral melatonin. C max, t 1/2 elimination, V d, CL and AUC 0-∞ were determined for intravenous melatonin.
  
  
  RESULTS
  Twelve male volunteers completed the study. Baseline melatonin plasma levels did not differ significantly between the study days (P = 0.067). Mean (SD) t 1/2 absorption of oral melatonin was 6.0 (3.1) min. Mean t max was 40.8 (17.8) min with a median (IQR) C max of 3550.5 (2500.5-8057.5) pg ml(-1). Mean t 1/2 elimination was 53.7 (7.0) min. Median absolute bioavailability was 2.5 (1.7-4.7) %. Median C max after short iv infusion of melatonin was 389,875.0 (174,775.0-440,362.5) pg ml(-1). Mean t 1/2 elimination was 39.4 (3.6) min, mean V d 1.2 (0.6) l kg(-1) and mean CL 0.0218 (0.0102) l min(-1) kg(-1).
  
  
  CONCLUSIONS
  This cohort crossover study estimated pharmacokinetics of oral and iv melatonin, respectively in healthy volunteers. Bioavailability of oral melatonin was only 3 %.
  
  
  BACKGROUND
  Eudra-CT number: 2013-000205-23 (initial registration 27.03.2013). Clinicaltrials.gov Identifier: NCT01923974 (initial registration 08.08.2013).
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark. lphandersen@gmail.com.
authors.forename: Lars P H
authors.initials: LP
authors.lastname: Andersen
authors.affiliation: Multidisciplinary Pain Center 7612, Neuroscience Center, Rigshospitalet, Copenhagen, DK-2100, Denmark. mads.u.werner@gmail.com.
authors.forename: Mads U
authors.initials: MU
authors.lastname: Werner
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, DK-2100, Denmark. rosenkilde@sund.ku.dk.
authors.forename: Mette M
authors.initials: MM
authors.lastname: Rosenkilde
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark. kxq761@alumni.ku.dk.
authors.forename: Nathja G
authors.initials: NG
authors.lastname: Harpsøe
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark. Hanne.Fuglsang@regionh.dk.
authors.forename: Hanne
authors.initials: H
authors.lastname: Fuglsang
authors.affiliation: Department of Surgery D, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark. Jacob.Rosenberg@regionh.dk.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rosenberg
authors.affiliation: Department of Surgery, Roskilde and Køge Hospital, University of Copenhagen, Roskilde, DK-4000, Denmark. igo@regionsjaelland.dk.
authors.forename: Ismail
authors.initials: I
authors.lastname: Gögenur
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*; D001682:Biological Availability; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D015331:Cohort Studies; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007408:Intestinal Absorption; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000975:Antioxidants; D002492:Central Nervous System Depressants; D008550:Melatonin