Metabolism of pravastatin sodium in isolated rat hepatocytes. II. Structure elucidation of the metabolites by n.m.r. spectroscopy

Xenobiotica. 1991 Mar;21(3):277-93. doi: 10.3109/00498259109039469.

Abstract

1. The structures, including stereochemistry, of the two major metabolites of pravastatin sodium in an isolated rat hepatocyte system, i.e. the 4'a alpha-glutathione conjugate (CM-1) and the 3',5'-dihydrodiol (CM-2), were determined by one- and two-dimensional n.m.r. spectroscopy. 2. The structures of two synthetic pravastatin epoxides, possible precursors of the metabolites, were also established. 3. One of the synthetic epoxides, 4'a beta, 5' beta-epoxide was converted to the pravastatin metabolite, 4'a alpha-glutathione conjugate (CM-1) by a rat liver cytosol system and is proposed as the common metabolic intermediate between pravastatin sodium and the metabolites, CM-1 and CM-2.

MeSH terms

  • Animals
  • Biotransformation
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / metabolism
  • Glutathione / metabolism
  • Heptanoic Acids / metabolism*
  • In Vitro Techniques
  • Liver / cytology
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Naphthalenes / metabolism*
  • Pravastatin
  • Rats
  • Spectrophotometry, Ultraviolet

Substances

  • Epoxy Compounds
  • Heptanoic Acids
  • Naphthalenes
  • Glutathione
  • Pravastatin