Disease relevance of Cholylsarcosine

• When a [3H]triolein emulsion with either cholylsarcosine or cholyltaurine was infused intraduodenally in biliary fistula rats, recovery of 3H in lymph was 52 +/- 10% (mean +/- SD) for cholylsarcosine and 52 +/- 11% for cholyltaurine [1].
• This study compared the effect of a natural conjugated bile acid mixture from ox bile with that of cholylsarcosine, a synthetic conjugated bile acid, on fat absorption and diarrhea in a patient with the short-bowel syndrome [2].
• Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 +/- 0.002; cholylglycine 0.101 +/- 0.007 EU/mL) compared with placebo (0.282 +/- 0.124, P <.001) [3].
• Rats with CCl(4)-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks [3].
• Cholylsarcosine, a new conjugated bile acid analogue that has been developed as a bile acid replacement agent, improves lipid absorption in animals with steatorrhea caused by bile acid malabsorption and intestinal resection [4].

High impact information on Cholylsarcosine

• Physicochemical and physiological properties of cholylsarcosine. A potential replacement detergent for bile acid deficiency states in the small intestine [1].
• In vitro, cholylsarcosine behaved as cholylglycine with respect to promoting lipolysis by lipase/colipase [1].
• RESULTS: Cholylsarcosine was lost rapidly from the enterohepatic circulation with a t1/2 of 0.5 days [5].
• It is concluded that cholylsarcosine is absorbed from the ileum, has an enterohepatic circulation, does not undergo appreciable deconjugation or dehydroxylation in these rodents, and is nontoxic [6].
• When cholylsarcosine was administered in the diet at 140 mumol/kg.day, it was well absorbed and underwent little biotransformation during enterohepatic cycling; however, both bacterial deconjugation and dehydroxylation (without deconjugation) occurred to a small extent [6].

Chemical compound and disease context of Cholylsarcosine

• Bile acid replacement therapy with cholylsarcosine for short-bowel syndrome [7].
• Four primary biliary cirrhosis patients, who, despite more than a year of ursodeoxycholic acid therapy, had one or more liver tests persistently equal to or greater than twice the upper limit of normal, received cholylsarcosine (12-15 mg/kg/day) in addition to ursodeoxycholic acid (13-15 mg/kg/day) for six weeks in an open label study [8].

Biological context of Cholylsarcosine

• Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%) [3].
• The potential of the nontoxic bile salt derivative, cholylsarcosine, to enhance the intestinal absorption of peptides was investigated in vitro and in situ [9].

Anatomical context of Cholylsarcosine

• Absorption of cholylsarcosine was much greater from the ileal segment (28-fold that of the duodenum under control conditions) and was enhanced with 1,25(OH)(2)D(3) treatment [10].

Gene context of Cholylsarcosine

• The physiological relevance of ASBT induction by 1,25(OH)(2)D(3) was assessed by measuring absorption of cholylsarcosine, a non-metabolized synthetic bile acid analog, from duodenal or ileal closed loops of the perfused rat small intestine preparation [10].
• Treatment with cholylsarcosine increased absorption of C14:0 by 23%-29%, of C16:0 by 59%-74%, of C18:0 by 125%-138%, and of unsaturated C18-fatty acids by 36%-45% [7].

Analytical, diagnostic and therapeutic context of Cholylsarcosine

• By nonaqueous titrimetry, the pKa' of cholylsarcosine was 3.7, only slightly lower than that of cholylglycine (3.9) [1].
• The efficacy of cholylsarcosine, a synthetic deconjugation-resistant and nonsecretory conjugated bile acid analog for the treatment of fat malabsorption caused by severe bile acid malabsorption, was assessed in an animal model [11].
• The results indicate that oral administration of cholylsarcosine improved dietary fat absorption in a canine model of severe bile acid malabsorption with associated steatorrhea and bile acid deficiency in the proximal small intestine [11].

References