Effect of withdrawal of pravastatin on biliary lipid composition in humans.
Abrupt withdrawal of HMG-CoA reductase inhibitors is associated with increased excretion of cholesterol into bile, but this phenomenon has not been investigated in humans. In order to evaluate whether patients interrupting these hypolipidemic drugs are at increased risk of forming gallstones, pravastatin (40 mg twice a day) or placebo was randomly administered to 16 bile fistula patients for 5 days. Biliary lipid composition was determined in basal conditions and for 5 consecutive days after drug withdrawal. Both biliary cholesterol concentration and saturation increased significantly on the second day after pravastatin withdrawal, but tended to decrease thereafter. Biliary bile acids and phospholipids were not affected. This short-lasting effect on biliary cholesterol excretion was probably the result of a transient increase of hepatic cholesterol synthesis by the up-regulated HMG-CoA reductase in the absence of the inhibitory drug. These results are consistent with the hypothesis that, also in humans, biliary cholesterol excretion could be dependent on the hepatic free cholesterol pool.
Muraca
M
M
Institute of Internal Medicine, University of Padua, Italy.
Baggio
G
G
Vilei
M T
MT
Martini
S
S
Cianci
V
V
Crepaldi
G
G
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D001652:Bile Ducts / Q000601:surgery; D002769:Cholelithiasis / Q000139:chemically induced*; D002784:Cholesterol / Q000378:metabolism*; D018752:Diet, Fat-Restricted; D004311:Double-Blind Method; D004322:Drainage; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D010743:Phospholipids / Q000378:metabolism; D017035:Pravastatin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D017035:Pravastatin