Stereoselective disposition of hydroxychloroquine and its metabolites in rats
Identifieur interne : 002B97 ( Main/Merge ); précédent : 002B96; suivant : 002B98Stereoselective disposition of hydroxychloroquine and its metabolites in rats
Auteurs : Yimin Wei [États-Unis] ; Gloria A. Nygard [États-Unis] ; Shari L. Ellertson [États-Unis] ; Shoukry K. W. Khalil [États-Unis]Source :
- Chirality [ 0899-0042 ] ; 1995.
Descripteurs français
- KwdFr :
- Animaux, Antipaludiques (administration et posologie), Antipaludiques (métabolisme), Antipaludiques (pharmacocinétique), Biotransformation, Caractères sexuels, Chromatographie en phase liquide à haute performance, Femelle, Hydroxychloroquine (administration et posologie), Hydroxychloroquine (métabolisme), Hydroxychloroquine (pharmacocinétique), Mâle, Rat Sprague-Dawley, Rats, Répartition dans les tissus, Stéréoisomérie.
- MESH :
- administration et posologie : Antipaludiques, Hydroxychloroquine.
- métabolisme : Antipaludiques, Hydroxychloroquine.
- pharmacocinétique : Antipaludiques, Hydroxychloroquine.
- Animaux, Biotransformation, Caractères sexuels, Chromatographie en phase liquide à haute performance, Femelle, Mâle, Rat Sprague-Dawley, Rats, Répartition dans les tissus, Stéréoisomérie.
English descriptors
- KwdEn :
- Animals, Antimalarials (administration & dosage), Antimalarials (metabolism), Antimalarials (pharmacokinetics), Biotransformation, Chromatography, High Pressure Liquid, Female, Hydroxychloroquine (administration & dosage), Hydroxychloroquine (metabolism), Hydroxychloroquine (pharmacokinetics), Male, Rats, Rats, Sprague-Dawley, Sex Characteristics, Stereoisomerism, Tissue Distribution.
- MESH :
- chemical , administration & dosage : Antimalarials, Hydroxychloroquine.
- chemical , metabolism : Antimalarials, Hydroxychloroquine.
- chemical , pharmacokinetics : Antimalarials, Hydroxychloroquine.
- Animals, Biotransformation, Chromatography, High Pressure Liquid, Female, Male, Rats, Rats, Sprague-Dawley, Sex Characteristics, Stereoisomerism, Tissue Distribution.
Abstract
Racemic hydroxychloroquine‐sulfate (HCQ‐sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue. The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender‐specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times. © 1995 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/chir.530070807
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Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue. The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender‐specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times. © 1995 Wiley‐Liss, Inc.</div></front></TEI><double doi="10.1002/chir.530070807"><ISTEX><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stereoselective disposition of hydroxychloroquine and its metabolites in rats</title><author><name sortKey="Wei, Yimin" sort="Wei, Yimin" uniqKey="Wei Y" first="Yimin" last="Wei">Yimin Wei</name></author><author><name sortKey="Nygard, Gloria A" sort="Nygard, Gloria A" uniqKey="Nygard G" first="Gloria A." last="Nygard">Gloria A. Nygard</name></author><author><name sortKey="Ellertson, Shari L" sort="Ellertson, Shari L" uniqKey="Ellertson S" first="Shari L." last="Ellertson">Shari L. Ellertson</name></author><author><name sortKey="Khalil, Shoukry K W" sort="Khalil, Shoukry K W" uniqKey="Khalil S" first="Shoukry K. W." last="Khalil">Shoukry K. W. Khalil</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B989BA0CBE582D98AED63117835717A354D19789</idno><date when="1995" year="1995">1995</date><idno type="doi">10.1002/chir.530070807</idno><idno type="url">https://api.istex.fr/ark:/67375/WNG-TPBSLQSD-R/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000036</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000036</idno><idno type="wicri:Area/Istex/Curation">000036</idno><idno type="wicri:Area/Istex/Checkpoint">001930</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001930</idno><idno type="wicri:doubleKey">0899-0042:1995:Wei Y:stereoselective:disposition:of</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Stereoselective disposition of hydroxychloroquine and its metabolites in rats</title><author><name sortKey="Wei, Yimin" sort="Wei, Yimin" uniqKey="Wei Y" first="Yimin" last="Wei">Yimin Wei</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Dakota du Nord</region></placeName><wicri:cityArea>Pharmacokinetic Drug Analysis Laboratory and Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo</wicri:cityArea></affiliation></author><author><name sortKey="Nygard, Gloria A" sort="Nygard, Gloria A" uniqKey="Nygard G" first="Gloria A." last="Nygard">Gloria A. Nygard</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Dakota du Nord</region></placeName><wicri:cityArea>Pharmacokinetic Drug Analysis Laboratory and Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo</wicri:cityArea></affiliation></author><author><name sortKey="Ellertson, Shari L" sort="Ellertson, Shari L" uniqKey="Ellertson S" first="Shari L." last="Ellertson">Shari L. Ellertson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Dakota du Nord</region></placeName><wicri:cityArea>Pharmacokinetic Drug Analysis Laboratory and Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo</wicri:cityArea></affiliation></author><author><name sortKey="Khalil, Shoukry K W" sort="Khalil, Shoukry K W" uniqKey="Khalil S" first="Shoukry K. W." last="Khalil">Shoukry K. W. Khalil</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Dakota du Nord</region></placeName><wicri:cityArea>Pharmacokinetic Drug Analysis Laboratory and Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Dakota du Nord</region></placeName><wicri:cityArea>Correspondence address: Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Chirality</title><title level="j" type="alt">CHIRALITY</title><idno type="ISSN">0899-0042</idno><idno type="eISSN">1520-636X</idno><imprint><biblScope unit="vol">7</biblScope><biblScope unit="issue">8</biblScope><biblScope unit="page" from="598">598</biblScope><biblScope unit="page" to="604">604</biblScope><biblScope unit="page-count">7</biblScope><publisher>Alan R. Liss, Inc.</publisher><pubPlace>New York</pubPlace><date type="published" when="1995">1995</date></imprint><idno type="ISSN">0899-0042</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0899-0042</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Racemic hydroxychloroquine‐sulfate (HCQ‐sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue. The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender‐specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times. © 1995 Wiley‐Liss, Inc.</div></front></TEI></ISTEX><PubMed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Stereoselective disposition of hydroxychloroquine and its metabolite in rats.</title><author><name sortKey="Wei, Y" sort="Wei, Y" uniqKey="Wei Y" first="Y" last="Wei">Y. Wei</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105</wicri:regionArea><wicri:noRegion>Fargo 58105</wicri:noRegion></affiliation></author><author><name sortKey="Nygard, G A" sort="Nygard, G A" uniqKey="Nygard G" first="G A" last="Nygard">G A Nygard</name></author><author><name sortKey="Ellertson, S L" sort="Ellertson, S L" uniqKey="Ellertson S" first="S L" last="Ellertson">S L Ellertson</name></author><author><name sortKey="Khalil, S K" sort="Khalil, S K" uniqKey="Khalil S" first="S K" last="Khalil">S K Khalil</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1995">1995</date><idno type="RBID">pubmed:8593253</idno><idno type="pmid">8593253</idno><idno type="doi">10.1002/chir.530070807</idno><idno type="wicri:Area/PubMed/Corpus">000523</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000523</idno><idno type="wicri:Area/PubMed/Curation">000523</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000523</idno><idno type="wicri:Area/PubMed/Checkpoint">000494</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000494</idno><idno type="wicri:Area/Ncbi/Merge">001163</idno><idno type="wicri:Area/Ncbi/Curation">001163</idno><idno type="wicri:Area/Ncbi/Checkpoint">001163</idno><idno type="wicri:doubleKey">0899-0042:1995:Wei Y:stereoselective:disposition:of</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Stereoselective disposition of hydroxychloroquine and its metabolite in rats.</title><author><name sortKey="Wei, Y" sort="Wei, Y" uniqKey="Wei Y" first="Y" last="Wei">Y. Wei</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmaceutical Sciences, College of Pharmacy, North Dakota State University, Fargo 58105</wicri:regionArea><wicri:noRegion>Fargo 58105</wicri:noRegion></affiliation></author><author><name sortKey="Nygard, G A" sort="Nygard, G A" uniqKey="Nygard G" first="G A" last="Nygard">G A Nygard</name></author><author><name sortKey="Ellertson, S L" sort="Ellertson, S L" uniqKey="Ellertson S" first="S L" last="Ellertson">S L Ellertson</name></author><author><name sortKey="Khalil, S K" sort="Khalil, S K" uniqKey="Khalil S" first="S K" last="Khalil">S K Khalil</name></author></analytic><series><title level="j">Chirality</title><idno type="ISSN">0899-0042</idno><imprint><date when="1995" type="published">1995</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antimalarials (administration & dosage)</term><term>Antimalarials (metabolism)</term><term>Antimalarials (pharmacokinetics)</term><term>Biotransformation</term><term>Chromatography, High Pressure Liquid</term><term>Female</term><term>Hydroxychloroquine (administration & dosage)</term><term>Hydroxychloroquine (metabolism)</term><term>Hydroxychloroquine (pharmacokinetics)</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Sex Characteristics</term><term>Stereoisomerism</term><term>Tissue Distribution</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antipaludiques (administration et posologie)</term><term>Antipaludiques (métabolisme)</term><term>Antipaludiques (pharmacocinétique)</term><term>Biotransformation</term><term>Caractères sexuels</term><term>Chromatographie en phase liquide à haute performance</term><term>Femelle</term><term>Hydroxychloroquine (administration et posologie)</term><term>Hydroxychloroquine (métabolisme)</term><term>Hydroxychloroquine (pharmacocinétique)</term><term>Mâle</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Répartition dans les tissus</term><term>Stéréoisomérie</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Antimalarials</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antimalarials</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Antimalarials</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Antipaludiques</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antipaludiques</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" qualifier="pharmacocinétique" xml:lang="fr"><term>Antipaludiques</term><term>Hydroxychloroquine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biotransformation</term><term>Chromatography, High Pressure Liquid</term><term>Female</term><term>Male</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Sex Characteristics</term><term>Stereoisomerism</term><term>Tissue Distribution</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Biotransformation</term><term>Caractères sexuels</term><term>Chromatographie en phase liquide à haute performance</term><term>Femelle</term><term>Mâle</term><term>Rat Sprague-Dawley</term><term>Rats</term><term>Répartition dans les tissus</term><term>Stéréoisomérie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Racemic hydroxychloroquine-sulfate (HCQ-sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue. The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender-specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times.</div></front></TEI></PubMed></double></record>Pour manipuler ce document sous Unix (Dilib)
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