Synthesis and Pharmacokinetics of 1α-Hydroxyvitamin D3 Tritated at 22 and 23 Positins Showing High Spacific Radioactivity

A novel synthesis of a radioactive compound of 1α-hydroxyvitamin D3 (1α OHD3) (1) and its pharmacokinetics are described. Radioactive 1αOHD3 tritiated at 22 and 23 positions ([22, 23-3H4]1αOHD3) (5) was prepared via key reactions of the reduction of acetylenic side chain in the ketone (12) with tritium gas in the presence of palladium-charcoal and the subsequent Wittig reaction with the A-ring synthon (16). [22, 23-3H4]1αOHD3 (5) showed high specific radioactivity (111.5 Ci/mmol) and was used successfully in pharmacokinetics studeies with rats. In the pharmacockinetics studies, the plasma concentration level of the active form of vitamin D3, 1α, 25-dihydroxyvitamin D3 [1α, 25(OH)2D3], after oral or intravenous administration of [22, 23-3H4]1αOHD3 (5), showed longer half-life, lower maximum concentration, and lower area under the curve than those after treatment of 1α, 25(OH)2D3 tritiated at 26 and 27 positions (4). These results might suggest a beneficial therapeutic utility of 1αOHD3 (1) over the treatment of 1α, 25(OH)2D3 (2).