Document Detail


Disposition of the novel antitumour agent xanthenone-4-acetic acid in the mouse: identification of metabolites and routes of elimination.
MedLine Citation:
PMID:  7975728     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
1. Xanthenone-4-acetic acid (XAA) is an experimental antitumour agent which resembles flavone-8-acetic acid in its induction of cytokine synthesis, nitric oxide production and tumour haemorrhagic necrosis. We have investigated the excretion and metabolic fate of XAA in the BDF1 mouse. 2. XAA was administered intravenously at the maximal tolerated dose (1090 mumol/kg). Urine, plasma and bile were collected and subjected to analysis by hplc. Urine samples demonstrated labile metabolites which released XAA following incubation with beta-glucuronidase/sulphatase or at pH 9.0. The structures of isolated XAA metabolites were characterized by ms or 1H-NMR spectra at 400 MHz. 3. The major metabolite pathway of XAA involves conjugation with glucuronic acid, since the resulting metabolite, XAA acyl glucuronide, accounts for 25% of the dose excreted in the urine. Other metabolite pathways include alpha-oxidation of the acetic acid side chain and aromatic hydroxylation of the xanthenone ring.
Authors:
P Kestell; G W Rewcastle; B C Baguley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Xenobiotica; the fate of foreign compounds in biological systems     Volume:  24     ISSN:  0049-8254     ISO Abbreviation:  Xenobiotica     Publication Date:  1994 Jul 
Date Detail:
Created Date:  1994-12-08     Completed Date:  1994-12-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1306665     Medline TA:  Xenobiotica     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  635-47     Citation Subset:  IM    
Affiliation:
Cancer Research Laboratory, University of Auckland School of Medicine, New Zealand.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / metabolism*,  pharmacokinetics*
Bile / metabolism
Biliary Tract / metabolism
Chromatography, High Pressure Liquid
Dose-Response Relationship, Drug
Glucuronidase / metabolism
Hydrolysis
Male
Mice
Mice, Inbred Strains
Sulfatases / metabolism
Xanthenes / metabolism*,  pharmacokinetics*,  urine
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Xanthenes; 35614-21-2/xanthenone-4-acetic acid; EC 3.1.6.-/Sulfatases; EC 3.2.1.31/Glucuronidase

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