Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Marschall, HU; Wagner, M; Zollner, G; Fickert, P; Silbert, D; Gustafsson, U; Sahlin, S; Trauner, M.
Combined rifampicin and ursodeoxycholic acid treatment does not amplify rifampicin effects on hepatic detoxification and transport systems in humans.
Digestion. 2012; 86(3):244-249 Doi: 10.1159/000341420
Web of Science PubMed FullText FullText_MUG

 

Co-authors Med Uni Graz

Fickert Peter

Silbert-Wagner Dagmar

Trauner Michael

Wagner Martin

Zollner Gernot

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Abstract:

Rifampicin (RIFA) and ursodeoxycholic acid (UDCA) were found to stimulate different but complementary hepatobiliary detoxification pathways in gallstone patients. 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. 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. 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. 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. Copyright © 2012 S. Karger AG, Basel.

Find related publications in this database (using NLM MeSH Indexing)

Adult -

Aged -

Bile - chemistry

Bile Acids and Salts - analysis Bile Acids and Salts - biosynthesis

Biological Transport - drug effects

Biopsy -

Cholagogues and Choleretics - administration & dosage Cholagogues and Choleretics - pharmacokinetics

Cholelithiasis - drug therapy Cholelithiasis - metabolism Cholelithiasis - pathology

Dose-Response Relationship, Drug -

Drug Therapy, Combination -

Enzyme Inhibitors - administration & dosage Enzyme Inhibitors - pharmacokinetics

Female -

Humans -

Inactivation, Metabolic -

Liver - drug effects Liver - metabolism Liver - pathology

Male -

Middle Aged -

Rifampin - administration & dosage Rifampin - pharmacokinetics

Ursodeoxycholic Acid - administration & dosage Ursodeoxycholic Acid - pharmacokinetics

Young Adult -

Find related publications in this database (Keywords)

Fibroblast growth factor

Hepatic detoxification

Laparoscopic cholecystectomy

Primary biliary cirrhosis

Rifampicin

Ursodeoxycholic acid

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