Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity.
Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity.
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在 22 和 23 位氚化的 1 α-羟基维生素 D3 的合成和药代动力学显示出高比放射性。
DOI：
10.1248/cpb.48.215
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发表时间：
2000
影响因子：
1.7
通讯作者：
N. Kubodera
中科院分区：
文献类型：
--
作者：
A. Kawase;F. Ichikawa;N. Koike;S. Kamachi;W. Stumpf;Y. Nishii;N. Kubodera
描述了一种新的1 α -羟基维生素D3 (1 α OHD3)(1)放射性化合物的合成及其药代动力学。放射性的1 α OHD3在22和23位氚化（[22,23-(3)H4]1 α OHD3）(5)是通过在钯炭存在下与氚气还原酮（12）中的乙基侧链以及随后与a环合成子（16）的Wittig反应制备的。[22,23-(3)H4]1 α OHD3(5)具有较高的比放射性（111.5 Ci/mmol），成功用于大鼠药代动力学研究。在药代动力学研究中，口服或静脉给药[22,23-(3)H4]1 α OHD3后，活性形式维生素D3 1 α，25-二羟基维生素D3 [1 α，25(OH)2D3]的血药浓度水平(5)比26位和27位tritriated的1 α，25(OH)2D3治疗后的半衰期更长，最大浓度更低，曲线下面积更小(4)。这些结果可能表明1 α OHD3(1)比1 α，25(OH)2D3(2)的治疗效果更好。
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).