title: Effect of cholestyramine on bile acid pattern and synthesis during administration of ursodeoxycholic acid in man.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Medicine II, University of Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rust
authors.forename: G H
authors.initials: GH
authors.lastname: Sauter
authors.forename: M
authors.initials: M
authors.lastname: Oswald
authors.forename: J
authors.initials: J
authors.lastname: Büttner
authors.forename: G A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: G
authors.initials: G
authors.lastname: Paumgartner
authors.forename: U
authors.initials: U
authors.lastname: Beuers
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy*; D002783:Cholestenones / Q000097:blood; D002792:Cholestyramine Resin / Q000008:administration & dosage*; D002908:Chronic Disease; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D011537:Pruritus / Q000188:drug therapy*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage* / Q000097:blood
chemical_list: D001647:Bile Acids and Salts; D002783:Cholestenones; D002792:Cholestyramine Resin; C002656:7 alpha-hydroxy-4-cholesten-3-one; D014580:Ursodeoxycholic Acid