Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis

Pietro Invernizzi, Kenneth D R Setchell, Andrea Crosignani, Pier Maria Battezzati, Alberto Larghi, Nancy C. O'Connell, Mauro Podda

Research output: Contribution to journalArticle

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Abstract

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 (GCMS). 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.

Original languageEnglish (US)
Pages (from-to)320-327
Number of pages8
JournalHepatology
Volume29
Issue number2
DOIs
StatePublished - 1999
Externally publishedYes

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Ursodeoxycholic Acid
Biliary Liver Cirrhosis
Taurine
Bile Acids and Salts
Biotransformation
Lithocholic Acid
Feces
Bile
Gas Chromatography-Mass Spectrometry
Glycine
Cross-Over Studies
tauroursodeoxycholic acid
Liver Diseases
Urine
Therapeutics
Serum

ASJC Scopus subject areas

  • Hepatology

Cite this

Invernizzi, P., Setchell, K. D. R., Crosignani, A., Battezzati, P. M., Larghi, A., O'Connell, N. C., & Podda, M. (1999). Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. Hepatology, 29(2), 320-327. https://doi.org/10.1002/hep.510290220

Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. / Invernizzi, Pietro; Setchell, Kenneth D R; Crosignani, Andrea; Battezzati, Pier Maria; Larghi, Alberto; O'Connell, Nancy C.; Podda, Mauro.

In: Hepatology, Vol. 29, No. 2, 1999, p. 320-327.

Research output: Contribution to journalArticle

Invernizzi, P, Setchell, KDR, Crosignani, A, Battezzati, PM, Larghi, A, O'Connell, NC & Podda, M 1999, 'Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis', Hepatology, vol. 29, no. 2, pp. 320-327. https://doi.org/10.1002/hep.510290220
Invernizzi, Pietro ; Setchell, Kenneth D R ; Crosignani, Andrea ; Battezzati, Pier Maria ; Larghi, Alberto ; O'Connell, Nancy C. ; Podda, Mauro. / Differences in the metabolism and disposition of ursodeoxycholic acid and of its taurine-conjugated species in patients with primary biliary cirrhosis. In: Hepatology. 1999 ; Vol. 29, No. 2. pp. 320-327.
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