EFFECT OF WITHDRAWAL OF PRAVASTATIN ON BILIARY LIPID-COMPOSITION IN HUMANS

Abrupt withdrawal of HMG-CoA reductase inhibitors is associated with i ncreased excretion of cholesterol into bile, but this phenomenon has n ot been investigated in humans. In order to evaluate whether patients interrupting these hypolipidemic drugs are at increased risk of formin g gallstones, pravastatin (40 mg twice a day) or placebo was randomly administered to 16 bile fistula patients for 5 days. Biliary lipid com position was determined in basal conditions and for 5 consecutive days after drug withdrawal. Both biliary cholesterol concentration and sat uration increased significantly on the second day after pravastatin wi thdrawal, but tended to decrease thereafter. Biliary bile acids and ph ospholipids were not affected. This short-lasting effect on biliary ch olesterol excretion was probably the result of a transient increase of hepatic cholesterol synthesis by the up-regulated HMG-CoA reductase i n the absence of the inhibitory drug. These results are consistent wit h the hypothesis that, also in humans, biliary cholesterol excretion c ould be dependent on the hepatic free cholesterol pool.