title: The effects of the 3-hydroxy, 3-methylglutaryl coenzyme A reductase inhibitor pravastatin on bile composition and nucleation of cholesterol crystals in cholesterol gallstone disease.
abstract: 3-hydroxy,3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce biliary cholesterol saturation index (CSI) in duodenal bile in hypercholesterolemic patients and might be useful for gallstone dissolution. However, preliminary data suggest that these drugs are not effective in this respect. We therefore studied 33 patients with radiolucent gallstones in an opacifying gallbladder who were scheduled for elective cholecystectomy. Patients were treated with 40 mg pravastatin day-1 or placebo during the 3 weeks before surgery. Six patients could not be evaluated. Baseline characteristics (age, sex, body mass index, serum cholesterol, and the solitary/multiple gallstone ratio) were similar in both groups. Serum cholesterol fell by 39% in the pravastatin group (P < .001) and remained unchanged in the placebo group. Biliary cholesterol (9.5 +/- 1.3 vs. 14.3 +/- 1.5 mmol/L, P = .026), and phospholipid concentrations (24.8 +/- 3.9 vs. 36.7 +/- 3.9 mmol/L, P = .043) were lower in the pravastatin group. Although bile salt concentrations were lower in the pravastatin group (114 +/- 21 vs. 152 +/- 15 mmol/L), this difference was not significant. CSI was not different between both groups (142 +/- 27% [pravastatin] vs. 113 +/- 6% [placebo], P = NS). Cholesterol crystals were present in fresh bile in 7 of 13 patients in the pravastatin group and in 11 of 14 controls (P = NS). Nucleation time was comparable between the 2 groups (13 +/- 3 vs. 9 +/- 3 days, P = NS). Bile salt species and molecular species of phospholipids determined with high-performance liquid chromatography did not differ either between both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Gastroenterology, University Hospital, Utrecht, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Smit
authors.forename: K J
authors.initials: KJ
authors.lastname: van Erpecum
authors.forename: W
authors.initials: W
authors.lastname: Renooij
authors.forename: M F
authors.initials: MF
authors.lastname: Stolk
authors.forename: P
authors.initials: P
authors.lastname: Edgar
authors.forename: H
authors.initials: H
authors.lastname: Doornewaard
authors.forename: G P
authors.initials: GP
authors.lastname: Vanberge-Henegouwen
mesh_terms: D001646:Bile / Q000737:chemistry / Q000502:physiology*; D001647:Bile Acids and Salts / Q000032:analysis* / Q000378:metabolism; D015992:Body Mass Index; D002763:Cholecystectomy; D002769:Cholelithiasis / Q000188:drug therapy* / Q000503:physiopathology* / Q000601:surgery; D002784:Cholesterol / Q000032:analysis* / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000032:analysis / Q000097:blood; D010919:Placebos; D017035:Pravastatin / Q000627:therapeutic use*
chemical_list: D001647:Bile Acids and Salts; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010743:Phospholipids; D010919:Placebos; D002784:Cholesterol; D017035:Pravastatin