Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D-3 tritiated at 22 and 23 positions showing high specific radioactivity

A novel synthesis of a radioactive compound of Icr-hydroxyvitamin D-3 (1 al pha OHD3) (1) and its pharmacokinetics are described. Radioactive 1 alpha O HD3 tritiated at 22 and 23 positions ([22,23-H-3(4)] 1 alpha OHD3) (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-H-3(4)]1 a lpha OHD3 (5) showed high specific radioactivity (111.5 Ci/mmol) and was us ed successfully in pharmacokinetics studies with rats. In the pharmacokinet ics studies, the plasma concentration Level of the active form of vitamin D -3, 1 alpha,25-dihydroxy-vitamin D-3 [1 alpha,25(OH)(2)D-3)], after oral or intravenous administration of [22,23-H-3(4)] 1 alpha OHD3 (5), showed long er half-life, lower maximum concentration, and Lower area under the curve t han those after treatment of 1 alpha,25(OH)(2)D-3 tritiated at 26 and 27 po sitions (4). These results might suggest a beneficial therapeutic utility o f 1 alpha OHD3 (1) over the treatment of 1 alpha,25(OH)(2)D-3 (2).