Article Text
Abstract
BACKGROUND Stimulated bile acid synthesis preferentially utilises newly synthesised cholesterol, raising the posssiblity that combination of simvastatin (an inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator of bile acid synthesis) may result in reduced bile acid synthesis and greater enrichment of the pool with UDCA than that achieved with UDCA treatment alone.
AIMS To investigate the effect of simvastatin and UDCA given alone and in combination on serum and biliary lipid and biliary bile acid composition.
METHODS Eighteen patients with primary non-familial hypercholesterolaemia were studied during treatment with simvastatin 20 mg/day, UDCA 10 mg/kg/day, and a combination of the two drugs. Each regimen was given in random order for three months following a three month lead in period.
RESULTS Simvastatin significantly reduced serum low density lipoprotein (LDL) cholesterol but biliary cholesterol concentration remained unchanged. Combination of the two drugs had no synergistic effect on serum cholesterol concentration, but significantly increased the proportion of UDCA in the bile acid pool from 35% during UDCA to 48% during combination treatment (p<0.04).
CONCLUSIONS Results showed that: (1) simvastatin reduces serum LDL cholesterol but has no effect on biliary cholesterol concentration, supporting the concept that newly synthesised cholesterol is not the preferential source for biliary cholesterol; and (2) combination of simvastatin with UDCA has the predicted effect of enhancing the proportion of UDCA in the pool. This effect may be of benefit in the treatment of cholestatic liver diseases.
- simvastatin
- HMG-CoA reductase inhibitors
- ursodeoxycholic acid
- bile
- lipids
- hypercholesterolaemia
- simvastatin
Abbreviations
- HDL
- high density lipoprotein
- HMG-CoA reductase
- 3-hydroxy-3-methylglutaryl CoA reductase
- LDL
- low density lipoprotein
- SI
- saturation index
- UDCA
- ursodeoxycholic acid
- VLDL
- very low density lipoprotein
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- simvastatin
- HMG-CoA reductase inhibitors
- ursodeoxycholic acid
- bile
- lipids
- hypercholesterolaemia
- simvastatin
Abbreviations
- HDL
- high density lipoprotein
- HMG-CoA reductase
- 3-hydroxy-3-methylglutaryl CoA reductase
- LDL
- low density lipoprotein
- SI
- saturation index
- UDCA
- ursodeoxycholic acid
- VLDL
- very low density lipoprotein