| Metabolism and disposition of the antiviral nucleoside analogue AM365 in the isolated perfused rat liver. | |
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MedLine Citation:
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PMID: 16248840 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The present study was designed to investigate the hepatic disposition of the prodrug AM365 and the generated antiviral guanosine analogue, AM188 in the isolated perfused rat liver (IPL). The livers of rats (n=12) were isolated and perfused with Krebs-Henseleit pH 7.4 buffer to which AM365 was added as a bolus to achieve an initial perfusate concentration of 22.4 micromol/L. During the 120-min period after administration of AM365, bile was collected in 10-min intervals and perfusate was collected at the mid-point of these intervals. Concentrations of AM365 and AM188 in perfusate and bile were quantified by HPLC. Following administration of AM365, its concentration in perfusate declined and the concentration of AM188 increased; the sum of the molar concentrations remained constant. The clearance and hepatic extraction ratio of AM365 were 3.3+/-2.4 mL/min and 0.110+/-0.079, respectively. The cumulative amount of AM365 excreted in bile during the 120-min perfusion period was approximately 0.21% of the bolus dose, and 0.36% of the total amount of AM365 cleared by the liver during the period. The cumulative amount of AM188 excreted in bile was about 0.48% of the total amount of AM188 formed during the perfusion period. In conclusion, AM365 was metabolised to AM188, which appeared to be the only metabolite and was not further biotransformed. The biliary excretion of AM365 and AM188 was negligible. |
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Authors:
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Jiping Wang; Roger L Nation; Allan M Evans; Susan Cox; David Shackleford |
Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Current drug metabolism Volume: 6 ISSN: 1389-2002 ISO Abbreviation: Curr. Drug Metab. Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-10-26 Completed Date: 2005-12-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100960533 Medline TA: Curr Drug Metab Country: Netherlands |
Other Details:
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Languages: eng Pagination: 487-93 Citation Subset: IM |
Affiliation:
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Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Algorithms Animals Antiviral Agents / pharmacokinetics* Area Under Curve Bile / metabolism Chromatography, High Pressure Liquid Liver / metabolism* Male Nucleosides / pharmacokinetics* Rats Rats, Sprague-Dawley Tissue Distribution |
| Chemical | |
Reg. No./Substance:
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0/2-amino-9-(3- hydroxy-2-hydroxymethylprop-1-yl)purine; 0/Antiviral Agents; 0/Nucleosides |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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