Bioavailability of melatonin in humans after day-time administration of D-7 melatonin

Absolute bioavailability of the neurohormone melatonin (MLT) was studied in 12 young healthy volunteers (six males, six females) after administration at midday, on two separate occasions, of 23 mug by intravenous (i.v.) infus ion and 250 mug by oral solution of D-7 MLT, a molecule in which seven deut erium atoms replace seven hydrogen atoms. Exogenous (D-7) and endogenous (D -0) MLT were quantified simultaneously but separately by a highly specific assay: gas chromatography/negative ion chemical ionization mass spectrometr y, developed in our laboratory, which enabled us to go down to 0.5 pg/mL in plasma samples. After i.v. administration, the maximum plasma concentratio n (C-max) and the area under the plasma concentration-time curve (AUC) valu es were significantly different in male and female subjects, but there was no significant gender difference in total body clearance normalized to body weight: 1.27 +/- 0.20 L/h/kg and 1.18 +/- 0.22 L/h/kg for males and female s, respectively. The apparent terminal half-life (t(1/2z)) values were 36 /- 2 and 41 +/- 10 min, respectively. After oral administration, pharmacoki netic parameters used to quantify bioavailability were near three-fold grea ter in female subjects than in males, with large inter-individual variation s. The maximum plasma MLT concentration C-max +/- S.D. was found at 243.7 /- 124.6 pg/mL and 623.6 +/- 575.1 pg/mL for male and female subjects respe ctively, while the mean values for AUCs were 236 +/- 107 pg.h/mL and 701 +/ - 645 pg.h/mL. The absolute bioavailability of MLT was from 1 to 37%: mean = 8.6 +/- 3.9% and 16.8 +/- 12.7% for male and female subjects, respectivel y. Copyright (C) 2000 John Wiley & Sons, Ltd.