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

Identifieur interne : 000029 ( Ncbi/Checkpoint ); précédent : 000028; suivant : 000030

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

Auteurs : J B Fourtillan [France] ; A M Brisson ; P. Gobin ; I. Ingrand ; J P Decourt ; J. Girault

Source :

RBID : pubmed:11038434

Mots-clés :

Abstract

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 microg by intravenous (i.v.) infusion and 250 microg by oral solution of D(7) MLT, a molecule in which seven deuterium 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 spectrometry, 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 concentration (C(max)) and the area under the plasma concentration-time curve (AUC) values 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 females, respectively. The apparent terminal half-life (t(1/2(z))) values were 36+/-2 and 41+/-10 min, respectively. After oral administration, pharmacokinetic parameters used to quantify bioavailability were near three-fold greater in female subjects than in males, with large inter-individual variations. 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 respectively, 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, respectively.


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pubmed:11038434

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<div type="abstract" xml:lang="en">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 microg by intravenous (i.v.) infusion and 250 microg by oral solution of D(7) MLT, a molecule in which seven deuterium 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 spectrometry, 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 concentration (C(max)) and the area under the plasma concentration-time curve (AUC) values 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 females, respectively. The apparent terminal half-life (t(1/2(z))) values were 36+/-2 and 41+/-10 min, respectively. After oral administration, pharmacokinetic parameters used to quantify bioavailability were near three-fold greater in female subjects than in males, with large inter-individual variations. 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 respectively, 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, respectively.</div>
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