METABOLISM OF PRAVASTATIN SODIUM IN ISOLATED RAT HEPATOCYTES .1. GLUTATHIONE CONJUGATE FORMATION REACTION

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' 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.