Synthesis of [3 beta-3H]-3-epivitamin D3 and its metabolism in the rat.

3-Epivitamin D3, the 3 alpha epimer of vitamin D3, was synthesized, and its biological activity in the rat was evaluated. It was found to be approximately 4 times less active on a weight basis than vitamin D3 with respect to intestinal calcium transport, bone calcium mobilization, and calcification score as determined by the line-test assay. Tritiated 3-epivitamin D3 was prepared, and its metabolism in the rat was compared with that of vitamin D3 to investigate the reasons for this diminished activity. 3-Epivitamin D3 was converted to two polar metabolites, for which the chromatographic properties and the origin of biosynthesis (in the liver and kidney, respectively) correspond to 25-hydroxy-3-epivitamin D3 and 1 alpha,25-dihydroxy-3-epivitamin D3. The fact that the concentration of 1 alpha,25-dihydroxy-3-epivitamin D3 in the intestine is half that of 1 alpha,25-dihydroxyvitamin D3 may be one explanation for the reduced biological activity of this epimer.