N-ethyl-tauroursodeoxycholic acid, a novel deconjugation-resistant bile salt analogue: effects of acute feeding in the rat.
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)
Angelico
M
M
Institute of Internal Medicine A Francaviglia, Catania University, Italy.
Mangiameli
A
A
Nistri
A
A
Baiocchi
L
L
Sofia
M
M
Maina
M
M
Di Martino
M
M
Blasi
A
A
D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004386:Duodenum; D007262:Infusions, Intravenous; D007267:Injections; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D001647:Bile Acids and Salts; C095396:N-ethyltauroursodeoxycholic acid; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine