维生素D类似物22-氧杂骨化三醇的体内代谢：侧链截断和17-羟基化的证据。
In vivo metabolism of the vitamin D analog, 22-oxacalcitriol: evidence for side-chain truncation and 17-hydroxylation.
作者信息
Ishigai M, Arai S, Ishitani Y, Kumaki K
机构信息
Drug Metabolism and Pharmacokinetics Laboratory, Chugai Pharmaceutical Co. Ltd., Tokyo, Japan.
出版信息
J Steroid Biochem Mol Biol. 1998 Sep;66(5-6):281-93. doi: 10.1016/s0960-0760(98)00061-2.
After intravenous administration of the vitamin D3 analog, 22-oxacalcitriol (OCT), to normal rats plasma metabolites were investigated by HPLC, GC-MS and LC-MS. Five side-chain oxidation metabolites, 24R(OH)OCT, 24S(OH)OCT, (25R)-26(OH)OCT, (25S)-26(OH)OCT and 24oxoOCT, were identified by comparison with the corresponding synthetic compounds. These side-chain oxidation metabolites were similar to those of calcitriol [1alpha,25(OH)2 vitamin D3] described previously. Besides these five metabolites, two unique side-chain cleavage metabolites, 20S(OH)-hexanor-OCT and 17,20S(OH)2-hexanor-OCT, were identified as main metabolites in plasma by GC-MS and LC-MS using a specific chemical reaction. Our studies suggest that OCT is extensively metabolized and circulates in blood as a number of metabolites as well as unchanged OCT. This metabolism includes both unique pathways of C23-O22 cleavage and 17-hydroxylation, in addition to the side-chain oxidation metabolites similar to those of 1alpha,25-(OH)2D3.
给正常大鼠静脉注射维生素D3类似物22-氧杂骨化三醇（OCT）后，通过高效液相色谱（HPLC）、气相色谱-质谱联用（GC-MS）和液相色谱-质谱联用（LC-MS）对血浆代谢物进行了研究。通过与相应的合成化合物比较，鉴定出了五种侧链氧化代谢物，即24R(OH)OCT、24S(OH)OCT、(25R)-26(OH)OCT、(25S)-26(OH)OCT和24氧代OCT。这些侧链氧化代谢物与先前描述的骨化三醇[1α,25(OH)2维生素D3]的代谢物相似。除了这五种代谢物外，还通过GC-MS和LC-MS利用特定化学反应鉴定出了两种独特的侧链裂解代谢物，即20S(OH)-降碳-OCT和17,20S(OH)2-降碳-OCT，它们是血浆中的主要代谢物。我们的研究表明，OCT会广泛代谢，并以多种代谢物以及未改变的OCT形式在血液中循环。这种代谢不仅包括与1α,25-(OH)2D3类似的侧链氧化代谢物，还包括C23-O22裂解和17-羟基化的独特途径。
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