title: Disposition and metabolism of F6-1alpha,25(OH)2 vitamin D3 and 1alpha,25(OH)2 vitamin D3 in the parathyroid glands of rats dosed with tritium-labeled compounds.
abstract: 26,26,26,27,27,27-Hexafluoro-1alpha,25(OH)2 vitamin D3, a hexafluorinated analog of 1alpha,25(OH)2 vitamin D3, has been reported to be several times more potent than the parent compound with respect to some vitamin D actions. The reason for enhanced biological activity in the bones, kidneys, and small intestine appears to be related to F6-1alpha,25(OH)2 vitamin D3 metabolism to ST-232 (26,26,26,27,27,27-hexafluoro-1alpha,23S,25-trihydroxyvitamin D3), a bioactive 23S-hydroxylated form that is resistant to further metabolism. We compared the disposition and metabolism of [1beta-3H]F6-1alpha,25(OH)2 vitamin D3 and [1beta-3H]1alpha,25(OH)2 vitamin D3 in parathyroid glands of rats intravenously administered with labeled compounds at a dose of 10 microg/kg. In the [1beta-3H]F6-1alpha,25(OH)2 vitamin D3-dosed group, radioactivity was highly detected in the kidneys, parathyroid glands, and the small intestine. The radioactivity in the parathyroid glands remained high until 48 h postdosing, with values of 2.5, 8.4, and 14.6 times higher at 6, 24, and 48 h postdosing than after dosing with [1beta-3H] 1alpha,25(OH)2 vitamin D3. In the group given [1beta-3H]F6-1alpha,25(OH)2 vitamin D3, the unchanged compound was mainly detected with a small amount of ST-232 at 6 h postdosing. At the 24- and 48-h time points, over half of the radioactivity was observed as ST-232, and additionally, ST-233, the 23-oxo form, accounted for a small amount at the 48-h time point. The present study demonstrated local retention of [1beta-3H]F6-1alpha,25(OH)2 vitamin D3 and the bioactive metabolite ST-232 in parathyroid glands after intravenous administration. The findings may indicate one of the reasons for the higher potency of F6-1alpha,25(OH)2 vitamin D3 than 1alpha,25(OH)2 vitamin D3 in parathyroid.
authors.affiliation: Environmental Health Science Laboratory, Sumitomo Chemical Co Ltd, Osaka, Japan. komuro@sc.sumitomo-chem.co.jp
authors.forename: Setsuko
authors.initials: S
authors.lastname: Komuro
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanamaru
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006811:Humerus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010280:Parathyroid Glands / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution; D014316:Tritium; D005466:Fluorocarbons
chemical_list: D002117:Calcitriol; D014316:Tritium; C077906:26,26,26,27,27,27-hexafluoro-1,23,25-trihydroxyvitamin D3; C040488:26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3; D005466:Fluorocarbons