Document Detail


Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis.
MedLine Citation:
PMID:  9918905     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The clinical effectiveness of ursodeoxycholate in the treatment of liver disease may be limited by its poor absorption and extensive biotransformation. Because in vitro and in vivo studies suggest that the more hydrophilic bile acid tauroursodeoxycholate has greater beneficial effects than ursodeoxycholate, we have compared for the first time the absorption, metabolism, and clinical responses to these bile acids in patients with primary biliary cirrhosis (PBC). Twelve female patients with PBC were sequentially administered tauroursodeoxycholate and ursodeoxycholate (750 mg/d for 2 months) in a randomized, cross-over study. Bile acids were measured in serum, duodenal bile, urine, and feces by gas chromatography-mass spectrometry (GC-MS). Biliary ursodeoxycholate enrichment was higher during tauroursodeoxycholate administration (32.6% vs. 29.2% during ursodeoxycholate; P <.05). Lithocholic acid concentration was consistently higher in all biological fluids during ursodeoxycholate administration. Fecal bile acid excretion was the major route of elimination of both bile acids; ursodeoxycholate accounted for 8% and 23% of the total fecal bile acids during tauroursodeoxycholate and ursodeoxycholate administration, respectively (P <.05). Tauroursodeoxycholate was better absorbed than ursodeoxycholate, and, although it was partially deconjugated and reconjugated with glycine, it underwent reduced biotransformation to more hydrophobic metabolites. This comparative study suggests that tauroursodeoxycholate has significant advantages over ursodeoxycholate that may be of benefit for long-term therapy in PBC.
Authors:
P Invernizzi; K D Setchell; A Crosignani; P M Battezzati; A Larghi; N C O'Connell; M Podda
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  29     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-02-16     Completed Date:  1999-02-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  320-7     Citation Subset:  IM    
Affiliation:
Division of Internal Medicine, Ospedale San Paolo School of Medicine, University of Milan, Italy. pietro.invernizzi@unimi.it
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MeSH Terms
Descriptor/Qualifier:
Absorption
Adult
Aged
Bile / chemistry
Bile Acids and Salts / analysis,  blood,  urine
Cross-Over Studies
Duodenum / metabolism
Feces / chemistry
Female
Gas Chromatography-Mass Spectrometry
Humans
Lithocholic Acid / analysis,  blood,  urine
Liver Cirrhosis, Biliary / metabolism*
Middle Aged
Taurochenodeoxycholic Acid / analysis,  pharmacokinetics*
Ursodeoxycholic Acid / analysis,  pharmacokinetics*
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 128-13-2/Ursodeoxycholic Acid; 14605-22-2/tauroursodeoxycholic acid; 434-13-9/Lithocholic Acid; 516-35-8/Taurochenodeoxycholic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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