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Xenobiotica. 1992 May;22(5):487-98.

Metabolism of pravastatin sodium in isolated rat hepatocytes. I. Glutathione conjugate formation reaction.

Author information

1
Analytical and Metabolic Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.

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.

PMID:
1413864
DOI:
10.3109/00498259209053111
[Indexed for MEDLINE]

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