Bioavailability of melatonin in humans after day-time administration of D(7) melatonin.
Identifieur interne : 000248 ( PubMed/Curation ); précédent : 000247; suivant : 000249Bioavailability 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. GiraultSource :
- Biopharmaceutics & drug disposition [ 0142-2782 ] ; 2000.
English descriptors
- KwdEn :
- Administration, Oral, Adult, Anticonvulsants (administration & dosage), Anticonvulsants (blood), Anticonvulsants (pharmacokinetics), Area Under Curve, Biological Availability, Cross-Over Studies, Female, Gas Chromatography-Mass Spectrometry, Humans, Infusions, Intravenous, Male, Melatonin (administration & dosage), Melatonin (blood), Melatonin (pharmacokinetics), Metabolic Clearance Rate, Time Factors.
- MESH :
- chemical , administration & dosage : Anticonvulsants, Melatonin.
- chemical , blood : Anticonvulsants, Melatonin.
- chemical , pharmacokinetics : Anticonvulsants, Melatonin.
- Administration, Oral, Adult, Area Under Curve, Biological Availability, Cross-Over Studies, Female, Gas Chromatography-Mass Spectrometry, Humans, Infusions, Intravenous, Male, Metabolic Clearance Rate, Time Factors.
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.
PubMed: 11038434
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Bioavailability of melatonin in humans after day-time administration of D(7) melatonin.</title><author><name sortKey="Fourtillan, J B" sort="Fourtillan, J B" uniqKey="Fourtillan J" first="J B" last="Fourtillan">J B Fourtillan</name><affiliation wicri:level="1"><nlm:affiliation>CEMAF, 6 Avenue Mozart, 86000 Poitiers, France. labocemaf@cemaf.com</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CEMAF, 6 Avenue Mozart, 86000 Poitiers</wicri:regionArea></affiliation></author><author><name sortKey="Brisson, A M" sort="Brisson, A M" uniqKey="Brisson A" first="A M" last="Brisson">A M Brisson</name></author><author><name sortKey="Gobin, P" sort="Gobin, P" uniqKey="Gobin P" first="P" last="Gobin">P. Gobin</name></author><author><name sortKey="Ingrand, I" sort="Ingrand, I" uniqKey="Ingrand I" first="I" last="Ingrand">I. Ingrand</name></author><author><name sortKey="Decourt, J P" sort="Decourt, J P" uniqKey="Decourt J" first="J P" last="Decourt">J P Decourt</name></author><author><name sortKey="Girault, J" sort="Girault, J" uniqKey="Girault J" first="J" last="Girault">J. Girault</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:11038434</idno><idno type="pmid">11038434</idno><idno type="wicri:Area/PubMed/Corpus">000248</idno><idno type="wicri:Area/PubMed/Curation">000248</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Bioavailability of melatonin in humans after day-time administration of D(7) melatonin.</title><author><name sortKey="Fourtillan, J B" sort="Fourtillan, J B" uniqKey="Fourtillan J" first="J B" last="Fourtillan">J B Fourtillan</name><affiliation wicri:level="1"><nlm:affiliation>CEMAF, 6 Avenue Mozart, 86000 Poitiers, France. labocemaf@cemaf.com</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CEMAF, 6 Avenue Mozart, 86000 Poitiers</wicri:regionArea></affiliation></author><author><name sortKey="Brisson, A M" sort="Brisson, A M" uniqKey="Brisson A" first="A M" last="Brisson">A M Brisson</name></author><author><name sortKey="Gobin, P" sort="Gobin, P" uniqKey="Gobin P" first="P" last="Gobin">P. Gobin</name></author><author><name sortKey="Ingrand, I" sort="Ingrand, I" uniqKey="Ingrand I" first="I" last="Ingrand">I. Ingrand</name></author><author><name sortKey="Decourt, J P" sort="Decourt, J P" uniqKey="Decourt J" first="J P" last="Decourt">J P Decourt</name></author><author><name sortKey="Girault, J" sort="Girault, J" uniqKey="Girault J" first="J" last="Girault">J. Girault</name></author></analytic><series><title level="j">Biopharmaceutics & drug disposition</title><idno type="ISSN">0142-2782</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Administration, Oral</term><term>Adult</term><term>Anticonvulsants (administration & dosage)</term><term>Anticonvulsants (blood)</term><term>Anticonvulsants (pharmacokinetics)</term><term>Area Under Curve</term><term>Biological Availability</term><term>Cross-Over Studies</term><term>Female</term><term>Gas Chromatography-Mass Spectrometry</term><term>Humans</term><term>Infusions, Intravenous</term><term>Male</term><term>Melatonin (administration & dosage)</term><term>Melatonin (blood)</term><term>Melatonin (pharmacokinetics)</term><term>Metabolic Clearance Rate</term><term>Time Factors</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Anticonvulsants</term><term>Melatonin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Anticonvulsants</term><term>Melatonin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anticonvulsants</term><term>Melatonin</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Administration, Oral</term><term>Adult</term><term>Area Under Curve</term><term>Biological Availability</term><term>Cross-Over Studies</term><term>Female</term><term>Gas Chromatography-Mass Spectrometry</term><term>Humans</term><term>Infusions, Intravenous</term><term>Male</term><term>Metabolic Clearance Rate</term><term>Time Factors</term></keywords></textClass></profileDesc></teiHeader><front><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></front></TEI><pubmed><MedlineCitation Owner="NLM" Status="MEDLINE"><PMID Version="1">11038434</PMID><DateCreated><Year>2000</Year><Month>11</Month><Day>17</Day></DateCreated><DateCompleted><Year>2000</Year><Month>11</Month><Day>17</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0142-2782</ISSN><JournalIssue CitedMedium="Print"><Volume>21</Volume><Issue>1</Issue><PubDate><Year>2000</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Biopharmaceutics & drug disposition</Title><ISOAbbreviation>Biopharm Drug Dispos</ISOAbbreviation></Journal><ArticleTitle>Bioavailability of melatonin in humans after day-time administration of D(7) melatonin.</ArticleTitle><Pagination><MedlinePgn>15-22</MedlinePgn></Pagination><Abstract><AbstractText>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.</AbstractText><CopyrightInformation>Copyright 2000 John Wiley & Sons, Ltd.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Fourtillan</LastName><ForeName>J B</ForeName><Initials>JB</Initials><AffiliationInfo><Affiliation>CEMAF, 6 Avenue Mozart, 86000 Poitiers, France. labocemaf@cemaf.com</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brisson</LastName><ForeName>A M</ForeName><Initials>AM</Initials></Author><Author ValidYN="Y"><LastName>Gobin</LastName><ForeName>P</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Ingrand</LastName><ForeName>I</ForeName><Initials>I</Initials></Author><Author ValidYN="Y"><LastName>Decourt</LastName><ForeName>J P</ForeName><Initials>JP</Initials></Author><Author ValidYN="Y"><LastName>Girault</LastName><ForeName>J</ForeName><Initials>J</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016430">Clinical Trial</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>ENGLAND</Country><MedlineTA>Biopharm Drug Dispos</MedlineTA><NlmUniqueID>7911226</NlmUniqueID><ISSNLinking>0142-2782</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000927">Anticonvulsants</NameOfSubstance></Chemical><Chemical><RegistryNumber>JL5DK93RCL</RegistryNumber><NameOfSubstance UI="D008550">Melatonin</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000284">Administration, Oral</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000328">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D000927">Anticonvulsants</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000008">administration & dosage</QualifierName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000493">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D019540">Area Under Curve</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D001682">Biological Availability</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D018592">Cross-Over Studies</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D005260">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008401">Gas Chromatography-Mass Spectrometry</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D006801">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D007262">Infusions, Intravenous</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008297">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008550">Melatonin</DescriptorName><QualifierName MajorTopicYN="N" UI="Q000008">administration & dosage</QualifierName><QualifierName MajorTopicYN="N" UI="Q000097">blood</QualifierName><QualifierName MajorTopicYN="Y" UI="Q000493">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D008657">Metabolic Clearance Rate</DescriptorName></MeshHeading><MeshHeading><DescriptorName MajorTopicYN="N" UI="D013997">Time Factors</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2000</Year><Month>10</Month><Day>20</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2001</Year><Month>2</Month><Day>28</Day><Hour>10</Hour><Minute>1</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2000</Year><Month>10</Month><Day>20</Day><Hour>11</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">11038434</ArticleId><ArticleId IdType="pii">10.1002/1099-081X(200001)21:1<15::AID-BDD215>3.0.CO;2-H</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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