Pharmacokinetics of 1 -(2-Deoxy-2-fluoro-β-L-arabino-furanosyl)-5-methyluracil (L-FMAU) in Rats
Identifieur interne : 004147 ( Main/Exploration ); précédent : 004146; suivant : 004148Pharmacokinetics of 1 -(2-Deoxy-2-fluoro-β-L-arabino-furanosyl)-5-methyluracil (L-FMAU) in Rats
Auteurs : Jennifer D. Wright [Géorgie (pays)] ; Tianwei Ma [Géorgie (pays)] ; Chung K. Chu [Géorgie (pays)] ; F. Douglas Boudinot [Géorgie (pays)]Source :
- Pharmaceutical Research [ 0724-8741 ] ; 1995-09-01.
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Abstract
Abstract: Purpose. The objective of this study was to characterize the pharmacokinetics of 1 -(2-deoxy-2-fluoro-β-L-arabinofuranosyl)-5-methyluracil (L-FMAU), a nucleoside analogue with potent activity against the hepatitis B virus and the Epstein-Barr virus, in rats. Methods. Three doses of L-FMAU were administered intravenously (10, 25, and 50 mg/kg) to rats, and L-FMAU concentrations in plasma and urine were measured by HPLC. Pharmacokinetic parameters were generated by using area-moment analysis. Results. There were no significant differences in the pharmacokinetic parameters between the three doses (α < 0.05). Thus, the disposition of L-FMAU was linear over the dosage of 10 to 50 mg/kg. Plasma concentrations of L-FMAU declined rapidly with a terminal phase half-life of 1.33 ± 0.45 h (mean ± SD). Total clearance of L-FMAU was moderate, averaging 1.15 ± 0.28 L/h/kg. The fraction of compound excreted unchanged in urine was 0.59 ± 0.13. No glucuronide metabolite was found in the urine. The steady-state volume of distribution was 1.12 ± 0.26 L/kg indicating intracellular distribution of the compound. The fraction of L-FMAU bound to plasma proteins was approximately 15% and was independent of nucleoside concentration. Conclusions. The pharmacokinetics of L-FMAU in rats were independent of dose over the dosage range of 10 to 50 mg/kg.
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DOI: 10.1023/A:1016234009624
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Douglas Boudinot</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:7AA0C73528E8CC909DB764CAB823AC1FEA2C78EE</idno><date when="1995" year="1995">1995</date><idno type="doi">10.1023/A:1016234009624</idno><idno type="url">https://api.istex.fr/ark:/67375/1BB-K71DBWW0-Z/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000970</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000970</idno><idno type="wicri:Area/Istex/Curation">000970</idno><idno type="wicri:Area/Istex/Checkpoint">001838</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001838</idno><idno type="wicri:doubleKey">0724-8741:1995:Wright J:pharmacokinetics:of:deoxy</idno><idno type="wicri:Area/Main/Merge">004208</idno><idno type="wicri:Area/Main/Curation">004147</idno><idno type="wicri:Area/Main/Exploration">004147</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Pharmacokinetics of 1 -(2-Deoxy-2-fluoro-β-L-arabino-furanosyl)-5-methyluracil (L-FMAU) in Rats</title><author><name sortKey="Wright, Jennifer D" sort="Wright, Jennifer D" uniqKey="Wright J" first="Jennifer D." last="Wright">Jennifer D. Wright</name><affiliation wicri:level="3"><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Department of Pharmaceutics, College of Pharmacy, University of Georgia, 30602, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Ma, Tianwei" sort="Ma, Tianwei" uniqKey="Ma T" first="Tianwei" last="Ma">Tianwei Ma</name><affiliation wicri:level="3"><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Department of Medicinal Chemistry, College of Pharmacy, University of Georgia, 30602, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Chu, Chung K" sort="Chu, Chung K" uniqKey="Chu C" first="Chung K." last="Chu">Chung K. Chu</name><affiliation wicri:level="3"><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Department of Medicinal Chemistry, College of Pharmacy, University of Georgia, 30602, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author><author><name sortKey="Boudinot, F Douglas" sort="Boudinot, F Douglas" uniqKey="Boudinot F" first="F. Douglas" last="Boudinot">F. Douglas Boudinot</name><affiliation wicri:level="3"><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Department of Pharmaceutics, College of Pharmacy, University of Georgia, 30602, Athens</wicri:regionArea><placeName><settlement type="city">Athènes</settlement><region nuts="2" type="region">Attique (région)</region></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Pharmaceutical Research</title><title level="j" type="sub">An Official Journal of the American Association of Pharmaceutical Scientists</title><title level="j" type="abbrev">Pharm Res</title><idno type="ISSN">0724-8741</idno><idno type="eISSN">1573-904X</idno><imprint><publisher>Kluwer Academic Publishers-Plenum Publishers</publisher><pubPlace>New York</pubPlace><date type="published" when="1995-09-01">1995-09-01</date><biblScope unit="volume">12</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="1350">1350</biblScope><biblScope unit="page" to="1353">1353</biblScope></imprint><idno type="ISSN">0724-8741</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0724-8741</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>L-FMAU</term><term>hepatitis B virus</term><term>l-(2-deoxy-2-fluoro-β-L-arabinofuranosyl)-5-methyluracil</term><term>nucleoside</term><term>pharmacokinetics</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Purpose. The objective of this study was to characterize the pharmacokinetics of 1 -(2-deoxy-2-fluoro-β-L-arabinofuranosyl)-5-methyluracil (L-FMAU), a nucleoside analogue with potent activity against the hepatitis B virus and the Epstein-Barr virus, in rats. Methods. Three doses of L-FMAU were administered intravenously (10, 25, and 50 mg/kg) to rats, and L-FMAU concentrations in plasma and urine were measured by HPLC. Pharmacokinetic parameters were generated by using area-moment analysis. Results. There were no significant differences in the pharmacokinetic parameters between the three doses (α < 0.05). Thus, the disposition of L-FMAU was linear over the dosage of 10 to 50 mg/kg. Plasma concentrations of L-FMAU declined rapidly with a terminal phase half-life of 1.33 ± 0.45 h (mean ± SD). Total clearance of L-FMAU was moderate, averaging 1.15 ± 0.28 L/h/kg. The fraction of compound excreted unchanged in urine was 0.59 ± 0.13. No glucuronide metabolite was found in the urine. The steady-state volume of distribution was 1.12 ± 0.26 L/kg indicating intracellular distribution of the compound. The fraction of L-FMAU bound to plasma proteins was approximately 15% and was independent of nucleoside concentration. Conclusions. The pharmacokinetics of L-FMAU in rats were independent of dose over the dosage range of 10 to 50 mg/kg.</div></front></TEI><affiliations><list><country><li>Géorgie (pays)</li></country><region><li>Attique (région)</li></region><settlement><li>Athènes</li></settlement></list><tree><country name="Géorgie (pays)"><region name="Attique (région)"><name sortKey="Wright, Jennifer D" sort="Wright, Jennifer D" uniqKey="Wright J" first="Jennifer D." last="Wright">Jennifer D. Wright</name></region><name sortKey="Boudinot, F Douglas" sort="Boudinot, F Douglas" uniqKey="Boudinot F" first="F. Douglas" last="Boudinot">F. Douglas Boudinot</name><name sortKey="Chu, Chung K" sort="Chu, Chung K" uniqKey="Chu C" first="Chung K." last="Chu">Chung K. Chu</name><name sortKey="Ma, Tianwei" sort="Ma, Tianwei" uniqKey="Ma T" first="Tianwei" last="Ma">Tianwei Ma</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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