Isolation and identification of a major metabolite of PNU-107859, an MMP inhibitor from the biliary fluid of rats

J Pharm Sci. 1999 Jul;88(7):705-8. doi: 10.1021/js980427s.


PNU-107859, an important representative structure in a novel class of matrix metalloproteinases (MMP) inhibitors known as thiadiazoles, was found to be quickly eliminated from rats. A major metabolite (approximately 10% of total dose) was found to be present in the bile of rats. The metabolite in question was isolated and purified from the bile fluids collected from six cannulated rats. From a total of approximately 75 mg of PNU-107859 administered to rats, 3.3 mg of the metabolite was recovered. The NMR and mass spectrometry results indicated that the metabolite is a glucuronide conjugate (1-deoxy-1beta-substituted D-glucopyranosiduronic acid) of the intact drug. Furthermore, the UV, MS, and NMR data established that the conjugate is located at the nitrogen alpha to the thiocarbonyl of the thiadiazole ring.

MeSH terms

  • Animals
  • Bile / metabolism*
  • Chromatography, High Pressure Liquid
  • Magnetic Resonance Spectroscopy
  • Male
  • Mass Spectrometry
  • Matrix Metalloproteinase Inhibitors*
  • Protease Inhibitors / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Thiadiazoles / metabolism*
  • Urea / analogs & derivatives*
  • Urea / metabolism


  • Matrix Metalloproteinase Inhibitors
  • PNU 107859
  • Protease Inhibitors
  • Thiadiazoles
  • Urea