Distribution and metabolism of F6-1,25(OH)2 Vitamin D3 and 1,25(OH)2 Vitamin D3 in the bones of rats dosed with tritium-labeled compounds

Abstract 26,26,26,27,27,27-Hexafluo-1,25(OH) 2 vitamin D 3 , the hexafluorinated analog of 1,25(OH) 2 vitamin D 3 , has been reported to be several times more potent than the parent compound regarding some vitamin D actions. The reason for enhanced biologic activity in the kidneys and small intestine appears to be related to F 6 -1,25(OH) 2 vitamin D 3 metabolism to ST-232, 26,26,26,27,27,27-hexafluoro-1α,23S,25-trihydroxyvitamin D 3 , a bioactive 23S-hydroxylated form that is resistant to further metabolism. Since F 6 -1,25(OH) 2 vitamin D 3 is considered to prevent osteoporotic decrease in bone mass by suppressing bone turnover, we here compared the distribution and metabolism of [1β- 3 H]F 6 -1,25(OH) 2 vitamin D 3 and [1β- 3 H]1,25(OH) 2 vitamin D 3 in bones of rats by autoradiography and radio-HPLC. In the dosed groups, radioactivity was detected locally in the metaphysis, the modeling site in bones. As compared with the [1β- 3 H]1,25(OH) 2 vitamin D 3 case, [1β- 3 H]F 6 -1,25(OH) 2 vitamin D 3 was significantly retained in this site, and moreover, it mainly persisted as unchanged compound and ST-232. These findings indicate that the reason for the higher potency of F 6 -1,25(OH) 2 vitamin D 3 than 1,25(OH) 2 vitamin D 3 in bones are linked with increased distribution and reduced metabolism.