Determination of dicumarol metabolites in bile of rats.
After intravenous administration of dicumarol-14C to rats, the bile excreted over the next 24 hr contained from 32 to 46% of the administered radioactivity. At least three primary metabolites and a small amount of unchanged dicumarol were present in the bile. Over 91% of the primary metabolites was converted to dicumarol and 7-hydroxydicumarol by hydrolysis with beta-glucuronidase. Some primary metabolites were hydrolyzed simply by acidification to pH 3 or by treatment under the acidic conditions utilized in the enzymatic hydrolysis. The three primary metabolites contain carboxylic acid groups, as indicated by their electrophoretic mobility-pH profiles, and some are simple glucuronides of dicumarol and 7-hydroxydicumarol. The possibility that others are derivatives of these compounds in which a coumarin lactone ring is opened cannot be ruled out. When the metabolites released by either acidification or enzymatic hydrolysis were chromatographed in n-butanol-3 M ammonia, artifacts were produced, presumably as a result of decomposition of 7-hydroxydicumarol. The question is raised whether a previously reported metabolite (B055) is an artifact.
D000818:Animals; D001646:Bile / Q000032:analysis* / Q000378:metabolism; D002854:Chromatography, Paper; D001728:Dicumarol / Q000031:analogs & derivatives / Q000032:analysis* / Q000378:metabolism; D004590:Electrophoresis, Paper; D005243:Feces / Q000032:analysis; D005966:Glucuronidase; D006868:Hydrolysis; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats
D001728:Dicumarol; D005966:Glucuronidase