Effects of long-term treatment with low-dose pravastatin on biliary lipid and bile acid composition in patients with nonfamilial hyperlipoproteinemia.
We tested the possibility that pravastatin, a competitive inhibitor of hepatic hydroxymethyl glutaryl coenzyme A (HMG CoA) reductase, would alter cholesterol saturation of gallbladder bile by decreasing its cholesterol saturation index and/or degree of fatty acyl chain unsaturation in lecithin. Eighteen patients with type IIa hyperlipoproteinemia were treated with pravastatin 10 mg/d for 12 months. Gallbladder bile samples were aspirated with a duodenal tube by stimulating gallbladder contraction with intramuscular administration of cerulein before and after treatment. Serum cholesterol level was significantly reduced by 20% after 3 months, and this level was maintained after 12 months. In contrast, the cholesterol saturation index of gallbladder bile was not altered after 3 months (1.52 +/- 0.20 v 1.70 +/- 0.24), but it decreased significantly after 12 months (0.95 +/- 0.11, P < .01). The degree of fatty acyl chain unsaturation tended to decrease, although this was not statistically significant except for the decrease in molar percent of linoleate after 3 months. These findings suggest that long-term treatment with an inhibitor of HMG CoA reductase improves bile lithogenicity even at a comparatively low dose, and can decrease the incidence and complications of cholesterol gallstones.
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001646:Bile / Q000737:chemistry* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000032:analysis* / Q000378:metabolism; D002108:Ceruletide / Q000494:pharmacology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006951:Hyperlipoproteinemias / Q000188:drug therapy / Q000378:metabolism*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000032:analysis; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D005227:Fatty Acids; D005765:Gastrointestinal Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D010713:Phosphatidylcholines; D002108:Ceruletide; D002784:Cholesterol; D017035:Pravastatin