| Biotransformation of topotecan in the isolated perfused rat liver: identification of three novel metabolites. | |
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MedLine Citation:
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PMID: 9703931 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study evaluates the metabolism of the anticancer drug topotecan (TPT) in the isolated perfused rat liver of male Wistar-rats. Using a sensitive high-performance liquid chromatography method, in bile TPT, its ring-opened hydroxycarboxylate form and three new metabolites could be quantified. Enzymatic hydrolysis of the metabolites with beta-glucuronidase and mass spectroscopy revealed the existence of glucuronidated TPT as well as unconjugated and glucuronidated bidesmethyl TPT. Biliary secretion of glucuronidated N-bidesmethyl TPT was fast reaching a maximum already after 15 min(30.6 +/- 15.1 pmol/g liver.min), whereas secretion of TPT, topotecan glucuronide and N-bidesmethyl TPT was delayed (maximum at 30 min: 431 +/- 19, 6.4 +/- 2.1 and 12.7 +/- 2.7 pmol/g liver.min, respectively). No release of TPT metabolites into the perfusate was detected. The amount of TPT, TPT glucuronide, N-bidesmethyl TPT and N-bidesmethyl TPT glucuronide excreted into bile during 60 min of perfusion was 2.10 +/- 0.483%, 0.031 +/- 0.006%, 0.058 +/- 0.013% and 0.108 +/- 0.012% of TPT cleared from the perfusate over 60 min, respectively. In conclusion we could identify three novel TPT metabolites, however, their overall metabolism in the rat liver is low. |
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Authors:
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P Platzer; S Schaden; T Thalhammer; G Hamilton; B Rosenberg; I Silgoner; W Jäger |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 18 ISSN: 0250-7005 ISO Abbreviation: Anticancer Res. Publication Date: 1998 Jul-Aug |
Date Detail:
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Created Date: 1998-09-01 Completed Date: 1998-09-01 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: GREECE |
Other Details:
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Languages: eng Pagination: 2695-700 Citation Subset: IM |
Affiliation:
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Institute of Pharmaceutical Chemistry, University of Vienna, Austria. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile / chemistry, metabolism Biotransformation Chromatography, High Pressure Liquid Glucuronates / analysis Kinetics Liver / metabolism* Male Molecular Structure Perfusion Rats Rats, Wistar Sensitivity and Specificity Time Factors Topotecan / pharmacokinetics* |
| Chemical | |
Reg. No./Substance:
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0/Glucuronates; 123948-87-8/Topotecan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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