Synthesis and intestinal metabolism of ursodeoxycholic acid conjugate with an antiinflammatory agent, 5-aminosalicylic acid

J Lipid Res. 1998 Aug;39(8):1641-6.

Abstract

5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesized in above 90% yield by adding a basic solution of 5-aminosalicylic acid into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with cholylglycine hydrolase and Clostridium perfringens, that deconjugate naturally occurring glycine and taurine conjugates of bile acids. However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was partially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid and 5-aminosalicylic acid. We believe that this unique conjugation of ursodeoxycholic acid with 5-aminosalicylic acid may facilitate the transport of both 5-aminosalicylic acid and ursodeoxycholic acid to the colon and may be useful for the treatment of colonic inflammatory bowel diseases, ulcerative colitis and Crohn's disease.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amidohydrolases / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biological Transport, Active
  • Clostridium perfringens / metabolism
  • Colonic Polyps / drug therapy
  • Colonic Polyps / metabolism
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / metabolism
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism*
  • Intestines / microbiology
  • Mesalamine / chemical synthesis*
  • Mesalamine / metabolism*
  • Mesalamine / therapeutic use
  • Rats
  • Ursodeoxycholic Acid / analogs & derivatives*
  • Ursodeoxycholic Acid / chemical synthesis
  • Ursodeoxycholic Acid / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Mesalamine
  • Ursodeoxycholic Acid
  • Amidohydrolases
  • choloylglycine hydrolase