Abstract 563 Poster Session I, Saturday, 5/1 (poster 302)

At present, 1α-hydroxyvitamin D3 (1α-OH-D3) is used as a prodrug of 1α,25dihydroxyvitamin D3 (1α,25(OH)2D3) for clinical treatment of many vitamin D related diseases like osteoporosis. Previous in vivo metabolism studies in rats indicated that 1α-OH-D3 is rapidly metabolized into 1α,25(OH)2D3. Recent in vitro metabolism studies using cultured bone cells and keratinocytes in our laboratory indicated that 1α,25(OH)2D3 is metabolized into 1α,25-dihydroxy-3-epivitamin D3 (1α,25(OH)2-3-epi-D3), a novel A-ring modified metabolite. In this study, we reinvestigated the in vivo metabolism of 1α-OH-D3 in rats. Rats on a regular rodent diet weighing about 350g were used in this study. Each rat was given 500 µg of 1α-OH-D3 intravenously. The rats were sacrificed at time intervals shown in the table and the blood was collected. The lipid extract of 5 ml of serum obtained from each rat was then subjected to a straight phase HPLC system directly. The vitamin D3 metabolites were detected using a photodiode array detector. All the vitamin D3 metabolites exhibiting the typical vitamin D cis triene chromophore were purified and the identity of each metabolite was achieved through its comigration with the authentic standard on two different HPLC systems. Serum concentrations of 1α-OH-D3 and its metabolites are quantified using HPLC assay and the results are shown in the table below. From the results, it becomes obvious for the first time that 1α,25(OH)2-3-epi-D3 is a major in vivo metabolite in rats receiving pharmacological amounts of 1α-OH-D3. At present, the biological role of 1α,25(OH)2-3-epi-D3 still remains to be elucidated.

Table 1 No caption available.
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