Document Detail

Effect of cholestyramine on bile acid pattern and synthesis during administration of ursodeoxycholic acid in man.
MedLine Citation:
PMID:  10651838     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Cholestyramine is the first-line treatment for cholestasis-induced pruritus and is prescribed along with ursodeoxycholic acid (UDCA) in patients with cholestatic liver diseases. Impairment of the intestinal absorption of endogenous hydrophobic bile acids by cholestyramine is well known. It is unclear, however, whether cholestyramine also impairs the absorption of the hydrophilic bile acid, UDCA, in man. AIMS: To study serum levels of UDCA and endogenous bile acids as well as endogenous bile acid synthesis during simultaneous or separate administration of UDCA and cholestyramine in vivo; and absorption of UDCA both in the presence and absence of its hydrophobic epimer, chenodeoxycholic acid (CDCA), by cholestyramine in vitro. PATIENTS AND METHODS: Five healthy subjects received UDCA (12.5 +/- 0.5 mg kg-1 daily) as a single dose for periods of 14 days with or without cholestyramine (4 g daily). Fasting serum levels of bile acids and of 7alpha-hydroxy-4-cholesten-3-one (alpha-HC), a measure of endogenous bile acid synthesis, were determined by gas chromatography and high pressure liquid chromatography, respectively. In vitro, bile acid solutions were incubated for 24 h in the presence or absence of cholestyramine, and bile acid concentrations were determined in the supernatant. RESULTS: Simultaneous administration of UDCA and cholestyramine in man led to a decrease of fasting serum levels of UDCA by 60% when compared to UDCA serum levels during administration of UDCA alone. In contrast, serum levels of endogenous bile acids were not affected and alpha-HC serum levels were found increased 2. 7-fold indicating stimulation of endogenous bile acid synthesis by cholestyramine. Administration of cholestyramine and UDCA at an interval of 5 h tended to diminish the effect of cholestyramine on UDCA serum levels. In vitro, conjugated and unconjugated UDCA were effectively bound by cholestyramine both in the presence and absence of hydrophobic bile acids. CONCLUSIONS: The results strongly support the recommendation to administer UDCA and cholestyramine at different times of day.
C Rust; G H Sauter; M Oswald; J Büttner; G A Kullak-Ublick; G Paumgartner; U Beuers
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  30     ISSN:  0014-2972     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-02-24     Completed Date:  2000-02-24     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  135-9     Citation Subset:  IM    
Department of Medicine II, University of Munich, Germany.
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MeSH Terms
Bile Acids and Salts / blood
Cholestasis, Intrahepatic / drug therapy*
Cholestenones / blood
Cholestyramine Resin / administration & dosage*
Chronic Disease
Drug Administration Schedule
Drug Therapy, Combination
Pruritus / drug therapy*
Ursodeoxycholic Acid / administration & dosage*,  blood
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholestenones; 11041-12-6/Cholestyramine Resin; 128-13-2/Ursodeoxycholic Acid; 3862-25-7/7 alpha-hydroxy-4-cholesten-3-one

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