title: Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolism.
abstract: BACKGROUND
  Treatment with ursodeoxycholic acid and also, to some degree, statins reduces cholesterol saturation of bile. The present study aimed [1] to study the effects of combined treatment with ursodeoxycholic acid and pravastatin on hepatic cholesterol metabolism and [2] to evaluate if the addition of pravastatin to ursodeoxycholic acid treatment has beneficial effects on the lipid composition of gallbladder bile in gallstone patients.
  
  
  METHODS
  Nineteen patients with cholesterol gallstones were subjected to combined treatment with ursodeoxycholic acid (500 mg bid) and pravastatin (20 mg bid) for three weeks before cholecystectomy. Eleven patients received ursodeoxycholic acid only and 20 untreated gallstone patients served as controls. Gallbladder bile was collected, and for both the patients receiving combined treatment and the controls a liver biopsy was also obtained peroperatively.
  
  
  RESULTS
  The cholesterol saturation of bile averaged 59% in the patients on combined treatment, 60% in the ursodeoxycholic acid-treated patients, and 130% in the untreated controls. In the patients receiving ursodeoxycholic acid, this bile salt constituted approximately 60% of all bile salts. The patients receiving combined treatment had reduced cholesterol synthesis, as reflected by a 45% reduction in serum lathosterol. The activity and the mRNA levels of cholesterol 7 alpha-hydroxylase and the mRNA levels for the low density lipoprotein-receptor were not significantly affected.
  
  
  CONCLUSIONS
  Pravastatin does not further reduce the cholesterol saturation of bile in gallstone patients treated with ursodeoxycholic acid, although hepatic cholesterol synthesis is inhibited. The study supports the important concept that de novo synthesized cholesterol is not particularly important for biliary cholesterol secretion in humans.
authors.affiliation: Karoliniska Institutet, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: C-G
authors.initials: CG
authors.lastname: Hillebrant
authors.forename: B
authors.initials: B
authors.lastname: Nyberg
authors.forename: U
authors.initials: U
authors.lastname: Gustafsson
authors.forename: S
authors.initials: S
authors.lastname: Sahlin
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
authors.forename: M
authors.initials: M
authors.lastname: Rudling
authors.forename: C
authors.initials: C
authors.lastname: Einarsson
mesh_terms: D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D002756:Cholagogues and Choleretics / Q000627:therapeutic use*; D002769:Cholelithiasis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D000924:Anticholesteremic Agents; D002756:Cholagogues and Choleretics; D008078:Cholesterol, LDL; D012333:RNA, Messenger; D011973:Receptors, LDL; D014580:Ursodeoxycholic Acid; C001521:lathosterol; D002784:Cholesterol; D017035:Pravastatin