title: Metabolism of pravastatin sodium in isolated rat hepatocytes. I. Glutathione conjugate formation reaction.
abstract: 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.
authors.affiliation: Analytical and Metabolic Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Muramatsu
authors.forename: K
authors.initials: K
authors.lastname: Miyaguchi
authors.forename: H
authors.initials: H
authors.lastname: Iwabuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: T
authors.initials: T
authors.lastname: Kinoshita
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Takahagi
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction; D005978:Glutathione / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D017035:Pravastatin / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; C077184:pravastatin dihydrodiol; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D017035:Pravastatin