Abstract
In two simvastatin (SV) metabolites the 6′ α-methyl of SV is oxidized to either 6′ β-CH 2OH (I) or 6′ β-COOH (II). A possible intermediate is 6′ exomethylene SV (III). When Sprague Dawley rats received an i.v. dose of [ 14C] III (1 mg/kg) metabolite II was excreted in bile. When dogs received an i.v. dose of [ 14C] III together with either [ 3H] SV (1 mg/kg) or its hydroxy acid form, ([ 3H] SVA) (10 mg/kg), both 3H and 14C I and II were excreted in bile. These results strongly indicate that I and II are secondary metabolites of SV formed from III perhaps via a common aldehyde intermediate.
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