| Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. | |
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MedLine Citation:
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PMID: 9918905 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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P Invernizzi; K D Setchell; A Crosignani; P M Battezzati; A Larghi; N C O'Connell; M Podda |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 29 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 1999 Feb |
Date Detail:
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Created Date: 1999-02-16 Completed Date: 1999-02-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 320-7 Citation Subset: IM |
Affiliation:
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Division of Internal Medicine, Ospedale San Paolo School of Medicine, University of Milan, Italy. pietro.invernizzi@unimi.it |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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