Little J M, Chari M V, Lester R
J Lipid Res. 1985 May;26(5):583-92.
[3-3H]Cholic acid glucuronide [7 alpha,12 alpha-dihydroxy-3 alpha-O-(beta-D-glucopyranosyluronate)-5 beta- cholan-24-oate] was synthesized and administered to rats prepared with either an external biliary fistula or a ligated bile duct. When bile fistula animals were given either microgram or milligram amounts of the glucuronide, biliary secretion of label was rapid and efficient: greater than 90% of the administered label was secreted within 60 min and total recovery of label in bile was 98.6 +/- 1.2%. Studies in which [14C]taurocholate was included in the dose indicated that this bile acid was secreted into bile significantly more rapidly than was the glucuronide. In animals with ligated bile ducts, urinary excretion was the major route of elimination: after 20 hr, 83.4 +/- 9.3% of the administered dose had been excreted in urine. Urinary excretion of cholate glucuronide was significantly more rapid than that of taurocholate. Gas-liquid chromatographic analysis of the methyl ester acetate derivatives of labeled compounds isolated from bile and urine by chromatography established that the bulk (greater than 70%) of the administered material was secreted in bile or excreted in urine as the intact cholate glucuronide. From these results, we conclude that the glucuronidation of cholic acid produces a derivative which is rapidly and effectively cleared from the circulation and excreted.
合成了[3-³H]胆酸葡糖醛酸苷[7α,12α-二羟基-3α-O-(β-D-吡喃葡糖醛酸基)-5β-胆烷-24-酸]，并将其给予制备了外胆管瘘或结扎胆管的大鼠。当给胆管瘘动物给予微克或毫克量的葡糖醛酸苷时，标记物的胆汁分泌迅速且高效：给药后60分钟内超过90%的标记物被分泌，胆汁中标记物的总回收率为98.6±1.2%。剂量中包含[¹⁴C]牛磺胆酸盐的研究表明，这种胆汁酸分泌到胆汁中的速度明显比葡糖醛酸苷快得多。在胆管结扎的动物中，尿排泄是主要的消除途径：20小时后，给药剂量的83.4±9.3%已通过尿液排泄。胆酸葡糖醛酸苷的尿排泄明显比牛磺胆酸盐快。通过气相色谱分析从胆汁和尿液中通过色谱分离得到的标记化合物的乙酸甲酯衍生物，确定给药物质的大部分（超过70%）以完整的胆酸葡糖醛酸苷形式分泌到胆汁中或通过尿液排泄。从这些结果，我们得出结论，胆酸的葡糖醛酸化产生了一种衍生物，它能迅速有效地从循环中清除并排泄。
