title: Metabolism of pravastatin sodium in isolated rat hepatocytes. II. Structure elucidation of the metabolites by n.m.r. spectroscopy.
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.
authors.affiliation: Analytical and Metabolic Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Yoda
authors.forename: H
authors.initials: H
authors.lastname: Kuwano
authors.forename: K
authors.initials: K
authors.lastname: Miyaguchi
authors.forename: S
authors.initials: S
authors.lastname: Muramatsu
authors.forename: H
authors.initials: H
authors.lastname: Takahagi
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: 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
chemical_list: D004852:Epoxy Compounds; D006538:Heptanoic Acids; D009281:Naphthalenes; D005978:Glutathione; D017035:Pravastatin