Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.