Jarnagin K, Zeng S Y, Phelps M, DeLuca H F
J Biol Chem. 1985 Nov 5;260(25):13625-30.
The time course of in vivo metabolism of 24,25-dihydroxyvitamin D3 in rats has been examined. Several tissues were surveyed in an effort to discover new metabolites of 24,25-dihydroxyvitamin D3 and to estimate the concentrations of previously identified metabolites. Rapidly growing male rats were dosed with 24,25-dihydroxyvitamin D3 orally until plasma concentrations of 24,25-dihydroxyvitamin D3 were at steady state. 24,25-Dihydroxyvitamin [3-3H]D3 was then administered. At 10 min and 1, 6, 15, 24, 96, and 192 h after dosing, the animals were killed, and plasma, liver, intestine, and bones were analyzed with a newly developed gradient straight-phase high performance liquid chromatography system. The high performance liquid chromatography system is capable of base-line resolution of most of the major vitamin D metabolites. 24,25-Dihydroxyvitamin D3 clearance from plasma, liver, and kidney but not intestine followed a two-compartment model. 24,25-Dihydroxyvitamin D3 disappeared from plasma with a half-life of 0.55 h (fast phase) and 73.8 h (slow phase). Only two lipid-soluble metabolites of 24,25-dihydroxyvitamin D3 were detected: 24-oxo-25-hydroxyvitamin D3 and 1,24,25-trihydroxyvitamin D3. These compounds circulate at very low concentrations in the plasma (50 pg/ml of plasma).
已对大鼠体内24,25 - 二羟基维生素D3的代谢时间进程进行了研究。对多个组织进行了检测，以发现24,25 - 二羟基维生素D3的新代谢产物，并估算先前已鉴定代谢产物的浓度。给快速生长的雄性大鼠口服24,25 - 二羟基维生素D3，直至血浆中24,25 - 二羟基维生素D3浓度达到稳态。然后给予[3 - 3H]24,25 - 二羟基维生素D3。给药后10分钟、1、6、15、24、96和192小时，处死动物，并用新开发的梯度正相高效液相色谱系统分析血浆、肝脏、肠道和骨骼。该高效液相色谱系统能够对大多数主要维生素D代谢产物进行基线分离。血浆、肝脏和肾脏而非肠道中24,25 - 二羟基维生素D3的清除遵循二室模型。24,25 - 二羟基维生素D3从血浆中消失，半衰期为0.55小时（快相）和73.8小时（慢相）。仅检测到24,25 - 二羟基维生素D3的两种脂溶性代谢产物：24 - 氧代 - 25 - 羟基维生素D3和1,24,25 - 三羟基维生素D3。这些化合物在血浆中的循环浓度非常低（血浆中50 pg/ml）。
