Metabolism of the hypolipidemic agent tiadenol in man and in the rat

Arzneimittelforschung. 1986 Apr;36(4):722-8.

Abstract

The metabolism of the hypolipidemic agent 1,10-bis(hydroxyethylthio)decane (tiadenol, Eulip) has been studied in vivo in man and in the rat and in vitro in the rat. Following oral administration, in both species tiadenol was completely absorbed, extensively metabolized by the liver and more than 95% of the dose was eliminated in this form via kidneys within 48 h. Insignificant was the excretion of the unchanged drug in urine (approximately 1%) as well as that of its metabolites in the feces. 8 metabolites were isolated from human or rat urine and their structures were elucidated by means of electron impact, field desorption and positive and negative fast atom bombardment mass spectrometry. Both in man and in the rat the main metabolic pathway was the oxidation of the thioether sulfur, followed by oxidation or conjugation of the primary alcohol group(s). The urinary excretion of S-oxidized metabolites and sulfoxidized carboxylic metabolites accounted for 75% of the dose and that of S-oxidized conjugated metabolites for 20%. Rat in vitro studies showed that hepatic microsomal cytochrome P-450-dependent monooxygenase catalyzes the S-oxidative pathway, which governs the in vivo elimination of the drug in both species. Thus cytochrome P-450 is the key enzyme in the hepatic detoxification of tiadenol.

MeSH terms

  • Adult
  • Animals
  • Biotransformation
  • Cytochrome P-450 Enzyme System / metabolism
  • Fatty Alcohols / metabolism*
  • Fatty Alcohols / urine
  • Feces / analysis
  • Humans
  • Hypolipidemic Agents / metabolism*
  • Hypolipidemic Agents / urine
  • Kinetics
  • Male
  • Mass Spectrometry
  • Microsomes, Liver / metabolism
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Species Specificity

Substances

  • Fatty Alcohols
  • Hypolipidemic Agents
  • tiadenol
  • Cytochrome P-450 Enzyme System