BIOLOGIC STUDIES OF CHOLESTANE-3,5,6-TRIOL AND ITS DERIVATIVES. III. THE METABOLIC FATE AND METABOLITES OF CHOLESTANE-3,5,6-TRIOL IN ANIMALS

¹ Biological Research Laboratories and Chemical Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan

The absorption, tissue distribution, fecal and biliary excretion and metabolites of labeled cholestane-3,5,6-triol (CT) and its 3,6-diformate, both potent antiatherogenic and hypocholesterolemic agents, were studied in rats and monkeys. The rate of intestinal absorption of CT and its 3,6-diformate was about one-fifth of that of cholesterol in rats with thoracic duct fistulas. The presence of cholesterol accelerated the absorption of CT and its 3,6-diformate. There was no appreciable accumulation of radioactivity in any particular tissues after the i.v. injection of labeled CT. Studies in animals, either intact or with biliary fistulas, showed that the radioactivity was excreted exclusively into the feces or the bile at a much higher excretion rate than cholesterol. Most of the fecal or biliary radioactivity was found in the bile acid fraction. The major biliary metabolite was isolated chromatographically and identified as 3,5,6-trihydroxycholanic acid. These results indicate that CT is rapidly eliminated via bile after conversion to bile acids entirely different from the usual ones derived from cholesterol.