Lovastatin alters biliary lipid composition and dissolves gallstones: a long-term study in prairie dogs.
Lovastatin, an inhibitor of the rate-limiting enzyme in cholesterol biosynthesis, is widely used to treat hypercholesterolemia. We investigated the long-term effects of lovastatin alone and in combination with ursodeoxycholic acid on biliary lipid composition and gallstone dissolution. Forty-two prairie dogs were fed 1.2% cholesterol diet for 5 weeks, and cholecystectomy was performed on 6 animals to confirm gallstones. The remaining animals were maintained on a 0.4% cholesterol diet and were randomized to receive placebo, lovastatin (3.3 mg/g diet), ursodeoxycholic acid (10 mg/g), or combination of both drugs. After 10 weeks, animals underwent cholecystectomy. Dissolution response to therapy was determined, and serum and biliary lipids were measured. All treatment groups had significant reductions in serum cholesterol. Lovastatin treatment reduced both hepatic and gallbladder bile cholesterol, altered bile acid composition, and induced a 79% total response compared to placebo. Although ursodeoxycholic treatment induced a 44% response, long-term combination treatment elevated both gallbladder bile cholesterol and calcium and failed to produce an augmented response. These data suggest that lovastatin therapy alone may promote gallstone dissolution in humans.
Abedin
Mohammad Z
MZ
Department of Surgery, MCP Hahnemann University, Philadelphia, Pennsylvania 19102, USA.
Narins
Seth C
SC
Park
Eun H
EH
Smith
Peter R
PR
Kirkwood
Kimberly S
KS
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002769:Cholelithiasis / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004347:Drug Interactions; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D012589:Sciuridae; D014580:Ursodeoxycholic Acid / Q000494:pharmacology
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014580:Ursodeoxycholic Acid; D002784:Cholesterol; D008148:Lovastatin