Effect of replacement therapy with cholylsarcosine on fat malabsorption associated with severe bile acid malabsorption. Studies in dogs with ileal resection.
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. In two dogs, the ileum and ileocecal valve were resected, causing severe diarrhea, steatorrhea, bile acid malabsorption, and progressive weight loss. Cholylsarcosine was administered as the water-soluble sodium salt by mixing with the dog food. Various doses were explored as well as varying intakes of dog food. Fat absorption was assessed by gravimetric measurement of fecal fat; a nonabsorbable recovery marker (polyethylene glycol mol wt 4000) was used to correct for incomplete fecal collections. Cholylsarcosine caused a 5- to 30-fold increase in fat absorption but had no significant effect on weight loss or fecal weight. Duodenal content was collected during digestion of a meal via a surgically placed Thomas cannula; the aspirates were dilute, acidic, and had a low bile acid concentration. The bile acid concentration increased modestly when cholylsarcosine was administered, but remained below the critical micellization concentration. 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. Studies with this compound in patients with nutritional problems because of steatorrhea and severe bile acid malabsorption appear warranted.
Longmire-Cook
S J
SJ
Department of Medicine, University of California, San Diego, La Jolla 92093.
Lillienau
J
J
Kim
Y S
YS
Schteingart
C D
CD
Danzinger
R G
RG
Esch
O
O
Hofmann
A F
AF
D000042:Absorption; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002793:Cholic Acids / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy / Q000378:metabolism; D004041:Dietary Fats / Q000493:pharmacokinetics*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005766:Gastrointestinal Contents / Q000737:chemistry / Q000187:drug effects; D007082:Ileum / Q000502:physiology*; D008286:Malabsorption Syndromes / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
D001647:Bile Acids and Salts; D002793:Cholic Acids; D004041:Dietary Fats; C061997:cholylsarcosine; D012521:Sarcosine