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

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.

• Authors: G A Allan, J I Gedge, A N R Nedderman, S J Roffey, H F Small, R Webster
• Journal: Xenobiotica; the fate of foreign compounds in biological systems (Xenobiotica) Vol. 36 Issue 5 Pg. 399-418 (May 2006) ISSN: 0049-8254 [Print] England
• PMID: 16854779 (Publication Type: Journal Article)

Chemical References

• Bone Morphogenetic Proteins
• Oxadiazoles
• Protease Inhibitors
• UK-383,367
• Metalloendopeptidases
• BMP1 protein, human
• Bmp1 protein, rat
• Bone Morphogenetic Protein 1

Topics

• Administration, Oral
• Animals
• Bone Morphogenetic Protein 1
• Bone Morphogenetic Proteins (antagonists & inhibitors, metabolism)
• Chromatography, Liquid
• Cicatrix (drug therapy)
• Dogs
• Humans
• Metalloendopeptidases (antagonists & inhibitors, metabolism)
• Oxadiazoles (administration & dosage, pharmacokinetics)
• Oxidation-Reduction
• Plasma
• Protease Inhibitors (administration & dosage, chemistry, pharmacokinetics)
• Radioactivity
• Rats
• Rats, Sprague-Dawley