Effect of long term simvastatin administration as an adjunct to ursodeoxycholic acid: evidence for a synergistic effect on biliary bile acid composition but not on serum lipids in humans

Background-Stimulated bile acid synthesis preferentially utilises newly syn thesised cholesterol, raising the posssiblity that combination of simvastat in tan inhibitor of cholesterol synthesis) with ursodeoxycholic acid (UDCA; a stimulator of bile acid synthesis) may result in reduced bile acid synth esis and greater enrichment of the pool with UDCA than that achieved with U DCA 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 w ere 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 orde r for three months following a three month lead in period. Results-Simvastatin significantly reduced serum low density lipoprotein (LD L) cholesterol but biliary cholesterol concentration remained unchanged. Co mbination of the two drugs had no synergistic effect on serum cholesterol c oncentration, but significantly increased the proportion of UDCA in the bil e acid pool from 35% during UDCA to 48% during combination treatment (p<0.0 4). Conclusions-Results showed that: (1) simvastatin reduces serum LDL choleste rol but has no effect on biliary cholesterol concentration, supporting the concept that newly synthesised cholesterol is not the preferential source f or biliary cholesterol and (2) combination of simvastatin: with UDCA has th e predicted effect of enhancing the proportion of UDCA in the pool. This ef fect may be of benefit in the treatment of cholestatic liver diseases.