BIOTRANSFORMATION OF PRAVASTATIN SODIUM(I) - MECHANISMS OF ENZYMATIC TRANSFORMATION AND EPIMERIZATION OF AN ALLYLIC HYDROXY GROUP OF PRAVASTATIN SODIUM

One of the major metabolites, R-416(3′α-OH), of pravastatin sodium(PV, 6′β-OH), and a minor metabolite, R-418(6′α-OH), were produced in rat liver cytosol in the presence of adenosine 3′-phosphate 5′-phosphosulfate as a cofactor. The reactions were inhibited by the inhibitors for sulfotransferases, and 18OH was introduced to the 3′α- and 6′α-positions of R-416 and R-418, respectively, by incubation with H2 18O. These results strongly suggested that PV was metabolically activated by sulfation at the 6′β-hydroxy group by sulfotransferases, followed by nucleophilic attack of hydroxy anions at the 3′α- or 6′α-position, to give R-416 or R-418, respectively. © 1993 Academic Press.