Document Detail


Combined rifampicin and ursodeoxycholic acid treatment does not amplify rifampicin effects on hepatic detoxification and transport systems in humans.
MedLine Citation:
PMID:  22964716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) were found to stimulate different but complementary hepatobiliary detoxification pathways in gallstone patients.
AIM: To study whether single drug effects are sustained or even enhanced by combination of both drugs and whether possible effects are mediated by circulating fibroblast growth factor 19 (FGF19), which has recently been identified as a master regulator of bile acid biosynthesis.
METHODS: 20 patients scheduled for laparoscopic cholecystectomy were randomized to a combination of UDCA (1 g/day during 3 weeks before surgery) and RIFA (600 mg/day during 1 week before surgery), or no treatment. Routine biochemistry, lipids, bile acid synthesis (7α-hydroxy-4-cholesten-3-one, C-4) and FGF19 were measured in serum. Bile acids were analyzed in serum and bile. A wedge liver biopsy was taken for determination of expression of hepatobiliary ABC transporters on mRNA and protein levels and of enzymes and regulatory transcription factors involved in the metabolism of biliary compounds on mRNA levels.
RESULTS: Combination treatment with both RIFA and UDCA significantly stimulated bile acid and bilirubin detoxification (CYP3A4, p < 0.001), conjugation (UGT1A1, p < 0.001) and elimination (MRP2, p < 0.05), as well as bile acid synthesis (p < 0.05), as compared to untreated controls. Notably, serum FGF19 levels in RIFA- and UDCA-treated patients did not differ from controls.
CONCLUSION: Combined treatment with RIFA and UDCA preserves the previously observed beneficial effects of single treatment with RIFA, including stimulation of bile acid synthesis. Most notably, the latter effect in humans is not mediated by FGF19.
Authors:
Hanns-Ulrich Marschall; Martin Wagner; Gernot Zollner; Peter Fickert; Dagmar Silbert; Ulf Gustafsson; Staffan Sahlin; Michael Trauner
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-09-05
Journal Detail:
Title:  Digestion     Volume:  86     ISSN:  1421-9867     ISO Abbreviation:  Digestion     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-30     Completed Date:  2013-04-23     Revised Date:  2014-05-26    
Medline Journal Info:
Nlm Unique ID:  0150472     Medline TA:  Digestion     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  244-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Bile / chemistry
Bile Acids and Salts / analysis,  biosynthesis
Biological Transport / drug effects
Biopsy
Cholagogues and Choleretics / administration & dosage,  pharmacokinetics
Cholelithiasis / drug therapy*,  metabolism,  pathology
Dose-Response Relationship, Drug
Drug Therapy, Combination
Enzyme Inhibitors / administration & dosage,  pharmacokinetics
Female
Humans
Liver / drug effects,  metabolism,  pathology
Male
Metabolic Detoxication, Drug
Middle Aged
Rifampin / administration & dosage,  pharmacokinetics*
Ursodeoxycholic Acid / administration & dosage,  pharmacokinetics*
Young Adult
Grant Support
ID/Acronym/Agency:
P 18613-B05//Austrian Science Fund FWF
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 0/Enzyme Inhibitors; 724L30Y2QR/Ursodeoxycholic Acid; VJT6J7R4TR/Rifampin

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


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