Effect of basic cholane derivatives on intestinal cholic acid metabolism: in vitro and in vivo activity

J Pharm Sci. 1992 Mar;81(3):237-40. doi: 10.1002/jps.2600810310.

Abstract

A representative series of hydroxy-5 beta-cholanyl-24-amines were tested both in vitro and in vivo with respect to their activity against the intestinal bacteria responsible for bile acid metabolism. For the in vitro studies, radiolabeled [14C]cholic acid was incubated with human stools both in aerobic and anaerobic conditions in the presence of the title compounds at a dose of 10 micrograms/mL, and the biotransformation of cholic acid into radiolabeled deoxycholic acid and other metabolites was followed by TLC-radiochromatography. Of the compounds studied, 3 alpha, 12 alpha-dihydroxy-5 beta-cholan-24-N-methylamine showed the highest activity. This compound was used for the in vivo studies and was shown to inhibit the formation of endogenous secondary bile acids when chronically administered to rats at a dose of 60 micrograms/day for 15 days. The treated rats showed an increased ratio of taurocholic acid (primary bile acid) to taurodeoxycholic acid (secondary bile acid) in bile, a fact further suggesting a potent antibacterial activity of the compound toward bacteria responsible for bile acid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Anaerobiosis
  • Animals
  • Bile Acids and Salts / metabolism
  • Cholanes / pharmacology*
  • Cholic Acids / metabolism*
  • Feces / microbiology
  • Humans
  • Intestinal Mucosa / metabolism*
  • Intestines / drug effects
  • Intestines / microbiology
  • Male
  • Rats
  • Rats, Inbred Strains
  • Taurocholic Acid / metabolism
  • Taurodeoxycholic Acid / metabolism

Substances

  • Bile Acids and Salts
  • Cholanes
  • Cholic Acids
  • Taurodeoxycholic Acid
  • Taurocholic Acid