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Bioavailability of melatonin in humans after day‐time administration of D7 melatonin

Identifieur interne : 000359 ( Istex/Corpus ); précédent : 000358; suivant : 000360

Bioavailability of melatonin in humans after day‐time administration of D7 melatonin

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

Source :

RBID : ISTEX:20DC831A3C9C35916E1C0A23339D91E80544CD5E

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 µg by intravenous (i.v.) infusion and 250 µg by oral solution of D7 MLT, a molecule in which seven deuterium atoms replace seven hydrogen atoms. Exogenous (D7) and endogenous (D0) 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 (Cmax) 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 Cmax±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. Copyright © 2000 John Wiley & Sons, Ltd.


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DOI: 10.1002/1099-081X(200001)21:1<15::AID-BDD215>3.0.CO;2-H

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ISTEX:20DC831A3C9C35916E1C0A23339D91E80544CD5E

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<title type="main" xml:lang="en">Bioavailability of melatonin in humans after day‐time administration of D
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melatonin</title>
<title type="short" xml:lang="en">BIOAVAILABILITY OF MELATONIN AFTER D
<sub>7</sub>
ADMINISTRATION</title>
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<p>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 µg by intravenous (i.v.) infusion and 250 µg by oral solution of D
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) 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
<sub>max</sub>
±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. Copyright © 2000 John Wiley & Sons, Ltd.</p>
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<abstract 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 µg by intravenous (i.v.) infusion and 250 µg by oral solution of D7 MLT, a molecule in which seven deuterium atoms replace seven hydrogen atoms. Exogenous (D7) and endogenous (D0) 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 (Cmax) 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 Cmax±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. Copyright © 2000 John Wiley & Sons, Ltd.</abstract>
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