title: Increased bioavailability of oral melatonin after fluvoxamine coadministration.
abstract: BACKGROUND
  Fluvoxamine, a selective serotonin reuptake inhibitor, is known to elevate melatonin serum concentrations. It has not been clear whether these effects might be attributed to an increased melatonin production or to an decreased elimination of melatonin. The latter hypothesis was tested by this study.
  
  
  METHODS
  Five healthy male volunteers (one CYP2D6 poor metabolizer) received 5 mg melatonin either with or without coadministration of 50 mg fluvoxamine. Serum concentrations of melatonin and fluvoxamine were assessed from 0 to 28 hours after melatonin intake.
  
  
  RESULTS
  Coadministration of fluvoxamine, on average, led to an 17-fold higher (P < .05) area under concentration-time curve (AUC) and a 12-fold higher (P < .01) serum peak concentration (Cmax) of melatonin. The terminal elimination half-life was not significantly affected. The AUC and Cmax of fluvoxamine were about three times higher and the half-life was about two times higher in the poor metabolizer. There was a correlation (r = 0.63; P < .01) between the melatonin and fluvoxamine serum concentrations. The poor metabolizer was found to have a more pronounced and longer-lasting effect of fluvoxamine on the pharmacokinetics of melatonin.
  
  
  CONCLUSIONS
  This study showed an increase in the bioavailability of oral melatonin by coadministration of fluvoxamine. The effects of fluvoxamine on the melatonin serum concentrations in patients with depression might therefore be caused by inhibition of the elimination of melatonin and not attributable to an increased production of melatonin.
authors.affiliation: Department of Psychiatry, University of Mainz, Germany. sepp@psychiatrie.klinik.uni-mainz.de
authors.forename: S
authors.initials: S
authors.lastname: Härtter
authors.forename: M
authors.initials: M
authors.lastname: Grözinger
authors.forename: H
authors.initials: H
authors.lastname: Weigmann
authors.forename: J
authors.initials: J
authors.lastname: Röschke
authors.forename: C
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D016666:Fluvoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D012016:Reference Values; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D019389:Cytochrome P-450 CYP2D6; D016666:Fluvoxamine; D008550:Melatonin; D017367:Selective Serotonin Reuptake Inhibitors