Increased bioavailability of oral melatonin after fluvoxamine coadministration

Background: Fluvoxamine, a selective serotonin reuptake inhibitor, is known to elevate melatonin serum concentrations. It has not been clear whether t hese 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) receive d 5 mg melatonin either with or without coadministration of 50 mg fluvoxami ne, 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 hig her (P < .05) area under concentration-time curve (AUC) and a 12-fold highe r (P < .01) serum peak concentration (C-max) of melatonin. The terminal eli mination half-life was not significantly affected. The AUC and C-max of flu voxamine were about three times higher and the half-life was about two time s higher in the poor metabolizer. There was a correlation (r = 0.63; P < .0 1:) between the melatonin and fluvoxamine serum concentrations. The poor me tabolizer was found to have: a more pronounced and longer-lasting effect of fluvoxamine on the pharmacokinetics of melatonin, Conclusion: This study showed an increase in the bioavailability of oral me latonin by coadministration of fluvoxamine. The effects of fluvoxamine on t he melatonin serum concentrations in patients with depression might therefo re be caused by inhibition of the elimination of melatonin and not attribut able to an increased production of melatonin.