5 alpha-Cholest-8(14)-en-3 beta-ol-15-one. In vivo conversion to cholesterol upon oral administration to a nonhuman primate.

ABSTRACT

The metabolism of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one (I), a potent inhibitor of cholesterol synthesis with marked hypocholesteremic activity, has been studied in a nonhuman primate. A mixture of [2,4-3H]-I and [4-14C]-cholesterol was administered to a male baboon in the form of a feedball. Blood was samples at 4, 8, 12, 16, and 24 hr. Detailed analyses of the plasma lipids indicated very rapid absorption of I (relative to cholesterol) and metabolism to cholesterol, cholesteryl esters, and esters of I. The labeled cholesterol was characterized by chromatographic techniques and by purification by way of its dibromide derivative. The levels of 3H in plasma associated with I, esters of I, cholesterol, and cholesteryl esters each showed a different time course. By 24 hr after the administration of [2,4-3H]-I, most of the 3H in plasma was associated with cholesterol and cholesteryl esters. The levels of total 3H and 14C in plasma at various times after the administration of the mixture of [2,4-3H]-I and [4-14C]-cholesterol differed markedly with 3H showing a maximum value at 4 hr and 14C showing a maximum value at 24 hr.