title: Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity.
abstract: A novel synthesis of a radioactive compound of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) (1) and its pharmacokinetics are described. Radioactive 1 alpha OHD3 tritiated at 22 and 23 positions ([22,23-(3)H4]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-(3)H4]1 alpha OHD3 (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, 1 alpha,25-dihydroxy-vitamin D3 [1 alpha,25(OH)2D3], after oral or intravenous administration of [22,23-(3)H4]1 alpha OHD3 (5), showed longer half-life, lower maximum concentration, and lower area under the curve than those after treatment of 1 alpha,25(OH)2D3 tritiated at 26 and 27 positions (4). These results might suggest a beneficial therapeutic utility of 1 alpha OHD3 (1) over the treatment of 1 alpha,25(OH)2D3 (2).
authors.affiliation: Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawase
authors.forename: F
authors.initials: F
authors.lastname: Ichikawa
authors.forename: N
authors.initials: N
authors.lastname: Koike
authors.forename: S
authors.initials: S
authors.lastname: Kamachi
authors.forename: W E
authors.initials: WE
authors.lastname: Stumpf
authors.forename: Y
authors.initials: Y
authors.lastname: Nishii
authors.forename: N
authors.initials: N
authors.lastname: Kubodera
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001345:Autoradiography; D002117:Calcitriol / Q000097:blood; D006207:Half-Life; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D007553:Isotope Labeling; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium
chemical_list: D006887:Hydroxycholecalciferols; D014316:Tritium; D002117:Calcitriol; C008088:alfacalcidol