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Xenobiotica
the fate of foreign compounds in biological systems
Volume 14, 1984 - Issue 4
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Original Article

Metabolism of nabumetone (BRL 14777) by various species including man

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Pages 327-337 | Received 10 Aug 1983, Published online: 30 Sep 2009
 

Abstract

1. Radiotracer methodology was used to study the metabolic fate of 4-(6-methoxy-2-naphthyl)-butan-2-one (nabumetone) after oral administration to rats, mice, rabbits, dogs, rhesus monkeys and healthy human subjects.

2. Parent compound was not detected in plasma and urine and the major circulating metabolite in all species was identified as 6-methoxy-2-naphthylacetic acid, a compound known to possess anti-inflammatory activity.

3. Metabolites were mainly excreted in urine from which four principal metabolites were isolated and identified by mass spectrometry and independent synthesis.

4. Pathways involving O-demethylation, reduction of the ketone group and oxidation of the butanone side-chain to acetic acid occurred in all species, but the ratios of the metabolic end-products tended to be species dependent. In the rat about half of the administered nabumetone was oxidized to the pharmacologically active acid metabolite.

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