Mikami T, Ohshima A, Mosbach E H, Cohen B I, Ayyad N, Yoshii M, Ohtani K, Kihira K, Schteingart C D, Hoshita T
Department of Surgery, Beth Israel Medical Center, New York, NY 10003, USA.
J Lipid Res. 1996 Jun;37(6):1189-97.
The metabolism of 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul), the sulfonate analogue of bishomochenodeoxycholic acid, and its effect on biliary bile acid composition were studied during chronic administration in the hamster. After oral administration of radiolabeled bishomoCDC-sul, more than 80% of the radioactivity was excreted into the feces within 7 days, both as the unchanged sulfonate (38.5%) and two more polar metabolites (50.0% and 11.5%). The half time of the fecal excretion was 1.6 days. In gallbladder bile, the unchanged sulfonate and its major metabolite accounted for 19.1% and 19.8% of total bile acids, respectively. In another experiment, hamsters were fed bishomoCDC-sul with antibiotics to evaluate the site of biotransformation. Even when the number of intestinal microorganisms was greatly reduced, the same three metabolites were found in the feces: bishomoCDC-sul (44.0%) and the two polar metabolites (30.8% and 25.1%). The major metabolite was isolated from feces of the hamsters fed bishomoCDC-sul without antibiotics. Its chemical structure was identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the 15 alpha-hydroxylated derivative, namely sodium 3 alpha,7 alpha,15 alpha-trihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate. These results indicate that after oral administration, the sulfonate analogue of bishomochenodeoxycholic acid underwent enterohepatic circulation like a natural bile acid and was transformed, in part, into the 15 alpha-hydroxylated derivative and another more polar metabolite in the liver of hamsters. There was no evidence that bishomoCDC-sul was dehydroxylated to a lithocholic acid analogue during enterohepatic cycling.
在仓鼠慢性给药期间，研究了双同鹅去氧胆酸的磺酸盐类似物3α,7α-二羟基-25,26-双高-5β-胆烷-26-磺酸盐（bishomoCDC-sul）的代谢及其对胆汁胆汁酸组成的影响。口服放射性标记的bishomoCDC-sul后，7天内超过80%的放射性以未改变的磺酸盐（38.5%）和另外两种极性更强的代谢物（50.0%和11.5%）形式排泄到粪便中。粪便排泄的半衰期为1.6天。在胆囊胆汁中，未改变的磺酸盐及其主要代谢物分别占总胆汁酸的19.1%和19.8%。在另一项实验中，给仓鼠喂食bishomoCDC-sul并同时使用抗生素，以评估生物转化的部位。即使肠道微生物数量大幅减少，在粪便中仍发现了相同的三种代谢物：bishomoCDC-sul（44.0%）和两种极性代谢物（30.8%和25.1%）。主要代谢物是从喂食不含抗生素的bishomoCDC-sul的仓鼠粪便中分离出来的。通过质谱和核磁共振光谱鉴定其化学结构为15α-羟基化衍生物，即3α,7α,15α-三羟基-25,26-双高-5β-胆烷-26-磺酸钠盐。这些结果表明，口服后，双同鹅去氧胆酸的磺酸盐类似物像天然胆汁酸一样进行肠肝循环，并在仓鼠肝脏中部分转化为15α-羟基化衍生物和另一种极性更强的代谢物。没有证据表明bishomoCDC-sul在肠肝循环过程中脱羟基化为石胆酸类似物。
