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Xenobiotica
the fate of foreign compounds in biological systems
Volume 24, 1994 - Issue 7
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Original Article

Disposition of the novel antitumour agent xanthenone-4-acetic acid in the mouse: Identification of metabolites and routes of elimination

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Pages 635-647 | Received 04 Oct 1994, Published online: 27 Aug 2009
 

Abstract

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 μmol/kg). Urine, plasma and bile were collected and subjected to analysis by hplc. Urine samples demonstrated labile metabolites which released XAA following incubation with β-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 α-oxidation of the acetic acid side chain and aromatic hydroxylation of the xanthenone ring.

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