• DOI:10.1080/004982597240019
• Corpus ID: 1808025

Metabolism of a bisphosphonate ester (PNU-91638) in rat.

@article{Slatter1997MetabolismOA,
  title={Metabolism of a bisphosphonate ester (PNU-91638) in rat.},
  author={John Gregory Slatter and Kenneth L. Feenstra and M J Hauer and Phillip E. Sanders and James J. Vrbanac and Graham Vaughan Scott and William Speed},
  journal={Xenobiotica; the fate of foreign compounds in biological systems},
  year={1997},
  volume={27 10},
  pages={
          1039-51
        }
}

• J. Slatter, K. L. Feenstra, +4 authors W. Speed
• Published 1997
• Chemistry, Biology
• Xenobiotica; the fate of foreign compounds in biological systems

1. Metabolites of the cyclic bisphosphonate ester, 4-[2,2'-bis-(5,5- dimethyl-1,3,2-dioxaphosphorinan-2-yl)] butanoyl-3-fluoro-benzene (PNU-91638) in bile or urine of the male Sprague-Dawley rat were characterized by mass spectrometry. The chronically bile duct/duodenal-cannulated male rats received a single oral dose of 100 mg/kg [13C] [14C]PNU-91638. Bile and urine samples were analysed for radioactivity and profiled by hplc with radiometric and UV detection. 2. The 0-28-h bile and urine accounted for 46.0 and 19.7% of dose respectively. The structures of radioactive peaks were investigated by ionspray and liquid secondary ion mass spectrometry (LSIMS) and LSIMS/MS analysis. 3. Major metabolites in urine included two regioisomeric phenol glucuronides, a gem methyl hydroxylated metabolite of the bisphosphonate heterocycle, a phenol metabolite, parent drug and a benzylic alcohol metabolite. Additional metabolites in bile included an unstable phenol/glutathione adduct (from a putative epoxide intermediate) with several minor isobaric regioisomers, and a carboxylic acid derived from the gem methyl hydroxylated bisphosphonate ring. 4. The structures proposed have not been confirmed by nmr due to discontinuation of the development of PNU-91638.