Synthesis and pharmacokinetics of 1α-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity

Article abstract of DOI:10.1248/cpb.48.215

A novel synthesis of a radioactive compound of 1α-hydroxyvitamin D₃ (1αOHD₃) (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 studies with rats. In the pharmacokinetics 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 1αOHD₁ (1) over the treatment of 1α,25(OH)₂D₃ (2).

Full text of DOI:10.1248/cpb.48.215

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