| Disposition of naproxen, naproxen acyl glucuronide and its rearrangement isomers in the isolated perfused rat liver. | |
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MedLine Citation:
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PMID: 11513245 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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1. An isolated perfused rat liver (IPRL) preparation was used to investigate separately the disposition of the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP), its reactive acyl glucuronide metabolite (NAG) and a mixture of NAG rearrangement isomers (isoNAG), each at 30 microg NAP equivalents ml perfusate (n = 4 each group). 2. Following administration to the IPRL, NAP was eliminated slowly in a log-linear manner with an apparent elimination half-life (t 1/2) of 13.4 +/- 4.4h. No metabolites were detected in perfusate, while NAG was the only metablolite present in bile in measurable amounts (3.9 +/- 0.8% of the dose). Following their administration to the IPRL, both NAG and isoNAG were rapidly hydrolysed (t 1/2 in perfusate = 57 +/- 3 and 75 +/- 14 min respectively). NAG also rearranged to isoNAG in the perfusate. Both NAG and isoNAG were excreted intact in bile (24.6 and 14.8% of the NAG and isoNAG doses, respectively). 3. Covalent NAP-protein adducts in the liver increased as the dose changed from NAP to NAG to isoNAG (0.20 to 0.34 to 0.48% of the doses, respectively). Similarly, formation of covalent NAP-protein adducts in perfusate were greater in isoNAG-dosed perfusions. The comparative results suggest that isoNAG is a better substrate for adduct formation with liver proteins than NAG. |
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Authors:
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A Lo; R S Addison; W D Hooper; R G Dickinson |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Xenobiotica; the fate of foreign compounds in biological systems Volume: 31 ISSN: 0049-8254 ISO Abbreviation: Xenobiotica Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-08-21 Completed Date: 2001-09-06 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 1306665 Medline TA: Xenobiotica Country: England |
Other Details:
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Languages: eng Pagination: 309-19 Citation Subset: IM |
Affiliation:
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Centre for Studies in Drug Disposition, The University of Queensland, Royal Brisbane Hospital, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acylation Animals Anti-Inflammatory Agents, Non-Steroidal / metabolism* Bile / metabolism Glucuronides / metabolism* Half-Life Hydrolysis Isomerism Kinetics Liver / metabolism* Male Naproxen / metabolism* Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Glucuronides; 22204-53-1/Naproxen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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