Metabolism of pravastatin sodium in isolated rat hepatocytes. II. Structure elucidation of the metabolites by n.m.r. spectroscopy.
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.
Nakamura
T
T
Analytical and Metabolic Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Yoda
K
K
Kuwano
H
H
Miyaguchi
K
K
Muramatsu
S
S
Takahagi
H
H
Kinoshita
T
T
D000818:Animals; D001711:Biotransformation; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006538:Heptanoic Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009281:Naphthalenes / Q000378:metabolism*; D017035:Pravastatin; D051381:Rats; D013056:Spectrophotometry, Ultraviolet
D004852:Epoxy Compounds; D006538:Heptanoic Acids; D009281:Naphthalenes; D005978:Glutathione; D017035:Pravastatin