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Xenobiotica
the fate of foreign compounds in biological systems
Volume 36, 2006 - Issue 5
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Research Article

Pharmacokinetics and metabolism of UK-383,367 in rats and dogs: A rationale for long-lived plasma radioactivity

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Pages 399-418 | Received 18 Nov 2005, Published online: 22 Sep 2008
 

Abstract

UK-383,367 (5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazole-3-carboxamide) is a novel procollagen C-proteinase inhibitor evaluated for the treatment of post-surgical dermal scarring. It is extensively metabolized in rat and dog absorption, distribution, metabolism and excretion studies, and a metabolic pathway for UK-383,367 was determined. A long-lived metabolite was identified in dog plasma. Data indicate that this metabolite results from the oxadiazole ring-cleavage-producing oxamic acid, oxamide and oxalic acid. Ion exclusion chromatography was used to identify these polar metabolites, which were unretained on a standard reversed-phase high-performance liquid chromatography system. The oxamide metabolite was identified as the long-lived radioactivity, which was observed in dog plasma.

Acknowledgements

Paul Fish and colleagues from the chemistry and biology departments are acknowledged.

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