The purpose of this study was to investigate the physicochemical/
biological properties and the effects of acute administration of
N-ethyl-tauroursodeoxycholic acid in bile-
fistula rats. In vitro determination of high-performance liquid chromatography mobility, octanol/ water partitioning,
cholesterol solubilizing capacity, and sensitivity to
enzyme deconjugation by bacteria and
cholylglycine-
hydroxylase were performed. In vivo determination of the following was also performed: (1) maximum secretory rate (SRmax) and choleretic/secretory properties during intravenous (IV) administration; (2) site/ extent of absorption, effects on bile flow,
lipid secretion, and biotransformations after intraduodenal infusion. N-ethyl-
tauroursodeoxycholate has a lipophilicity slightly higher than
tauroursodeoxycholate, close to
taurocholate, and similar
cholesterol solubilizing capacity. Deconjugation of N-ethyl-
tauroursodeoxycholate was 3.4 +/- 2.1% after 72 hours, that of
tauroursodeoxycholate was 100% after 24 hours. During IV infusion of 300 nmol/min/ 100g, biliary secretion of N-ethyl-tauroursodeoxycholic and tauroursodeoxycholic
acids averaged 185 +/- 76 (standard deviation) nmol/min/100 g and 221 +/- 77 nmol/min/ 100 g (not significant). Increasing infusion rates caused progressive enhancement of bile flow and
bile salt secretion until the SRmax was reached (1,305 +/- 240 nmol/min/ 100 g for
N-ethyl-tauroursodeoxycholic acid and 3,240 nmol/min/100 g for
tauroursodeoxycholate). The two
bile salts were similarly choleretic. IV feeding of N-ethyl-tauroursodeoxycholic promoted a greater
lipid secretion than
tauroursodeoxycholate. After intraduodenal feeding of 800 mumol, 38.8 +/- 14.0% and 43.4 +/- 12.4% of the two
bile salts were recovered in bile. No unconjugated
bile salts nor unusual metabolites were detected.(ABSTRACT TRUNCATED AT 250 WORDS)