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’ aβ, 5'β-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.