Metabolism of pravastatin sodium in isolated rat hepatocytes. I. Glutathione conjugate formation reaction

Xenobiotica. 1992 May;22(5):487-98. doi: 10.3109/00498259209053111.


1. The metabolic fate of pravastatin sodium (sodium (+)-(3R,5R)-3,5-dihydroxy-7-((1'S,2'S,6'S,8'S,8'aR)-6'-hydroxy-2'methyl- 8'-[(S)-2"-methylbutyryloxy]-1',2',6',7',8', 8'a-hexahydro-1'-naphthyl) heptanoate) was studied in isolated rat hepatocytes. 2. Two polar metabolites were isolated and identified as a glutathione conjugate and a dihydrodiol. 3. Both metabolites were formed via an epoxide which has been identified as the 4'a beta,5' beta-epoxide on the decalin moiety. 4. Formation of the glutathione conjugate was enzymic, while the dihydrodiol was formed by non-enzymic hydrolysis of the epoxide accompanied by the intramolecular migration of the double bond.

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / metabolism
  • Cytosol / metabolism
  • Enzyme Induction
  • Glutathione / metabolism*
  • Liver / cytology
  • Liver / enzymology
  • Liver / metabolism*
  • Male
  • Mass Spectrometry
  • Pravastatin / analogs & derivatives
  • Pravastatin / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Cytochrome P-450 Enzyme Inhibitors
  • pravastatin dihydrodiol
  • Cytochrome P-450 Enzyme System
  • Glutathione
  • Pravastatin