Schmassmann A, Fehr H F, Locher J, Lillienau J, Schteingart C D, Rossi S S, Hofmann A F
Department of Medicine, Kantonsspital Aarau, Switzerland.
Gastroenterology. 1993 Apr;104(4):1171-81. doi: 10.1016/0016-5085(93)90289-o.
Cholylsarcosine, the synthetic conjugate of cholic acid and sarcosine, is resistant to deconjugation-dehydroxylation during enterohepatic cycling in rodents and improves lipid absorption in a canine model of intestinal bile acid deficiency caused by distal intestinal resection. Experiments were performed to define its metabolism and effect on biliary secretion in humans.
The circulating bile acid pool was labeled with [14C]cholylsarcosine, and its turnover rate and biotransformation were determined by sampling bile daily. Cholylsarcosine (or cholyltaurine) was infused into the duodenum for 8 hours to define its effect on bile flow and biliary lipid secretion.
Cholylsarcosine was lost rapidly from the enterohepatic circulation with a t1/2 of 0.5 days. The compound was not biotransformed by hepatic or bacterial enzymes. Cholylsarcosine had choleretic activity similar to that of cholyltaurine but induced more phospholipid and cholesterol secretion than cholyltaurine in four or five subjects. Infusion of cholylsarcosine (or cholyltaurine) at a rate averaging 0.6 mumol.min-1.kg-1 gave a biliary recovery of 0.2 mumol.min-1.kg-1; this value is the Tmax for active ileal transport of conjugated bile acids in humans. Laboratory tests for liver injury remained within normal limits.
In humans, cholylsarcosine is not metabolized, is nontoxic, and has similar effects on biliary secretion as cholyltaurine. It appears safe to test in long-term studies the effect of cholylsarcosine on bile acid-deficiency states in humans.
胆酰肌氨酸，即胆酸与肌氨酸的合成共轭物，在啮齿动物的肠肝循环中对去共轭 - 去羟基化具有抗性，并且在由远端肠切除引起的肠道胆汁酸缺乏的犬模型中可改善脂质吸收。进行实验以确定其在人体内的代谢及对胆汁分泌的影响。
用[14C]胆酰肌氨酸标记循环胆汁酸池，通过每日采集胆汁来测定其周转率和生物转化。将胆酰肌氨酸（或胆酰牛磺酸）注入十二指肠8小时，以确定其对胆汁流量和胆汁脂质分泌的影响。
胆酰肌氨酸从肠肝循环中迅速消失，半衰期为0.5天。该化合物未被肝酶或细菌酶生物转化。在四或五名受试者中，胆酰肌氨酸具有与胆酰牛磺酸相似的利胆活性，但比胆酰牛磺酸诱导更多的磷脂和胆固醇分泌。以平均0.6 μmol·min-1·kg-1的速率输注胆酰肌氨酸（或胆酰牛磺酸）时，胆汁回收率为0.2 μmol·min-1·kg-1；该值是人体内共轭胆汁酸活性回肠转运的Tmax。肝损伤的实验室检查仍在正常范围内。
在人体内，胆酰肌氨酸不被代谢，无毒，并且对胆汁分泌的影响与胆酰牛磺酸相似。在长期研究中测试胆酰肌氨酸对人体胆汁酸缺乏状态的影响似乎是安全的。
