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

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-1 alpha,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 [1 beta-H-3]F-6-1,25(OH)(2) vitamin D-3 and [1 beta-H-3]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 [1 beta-H-3]1,25(OH)(2) vitamin D-3 case, [1 beta-H-3]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. (Steroids 63:505-510, 1998) (C) 1998 by Elsevier Science Inc.