Clofibrate treatment and bile cholesterol saturation: short-term and long-term effects and influence of combination with chenodeoxycholic acid

Abstract . In order to determine whether the clofibrate-induced increase in bile cholesterol saturation is transitory, duodenal bile samples were analysed from sixteen hyperlipoproteinaemic patients before and after 6 months to 2 years treatment with clofibrate, 2 g daily. Standardized dietary and weight conditions were obtained. In all but two subjects cholesterol saturation remained elevated (150 ± 7%, mean ± SEM) compared to pretreatment values (112 ± 6%, P < 0.01).
In nine of the patients, duodenal bile was obtained also after 6 weeks of treatment. Although two patients with increased saturation at 6 weeks displayed a return to basal values at 2 years, the majority showed no consistent changes between these two occasions.
Addition of chenodeoxycholic acid to clofibrate medication led to a normalization of cholesterol saturation (from 145 ± 9 to 89 ± 18%, P < 0.01) in eight out of nine patients studied. The serum levels of total cholesterol and triglycerides, very low density lipopro-tein and high density lipoprotein cholesterol were not significantly changed. However, the low density lipoprotein (LDL) cholesterol concentration was increased by 15–20% (from 4.8 ±0.3 to 5.7 ± 0.4 mmol/l, P <0.01).
It is concluded that clofibrate induces changes in biliary lipid composition which are consistent over at least 2 years of treatment. Possible measures to avoid these effects must therefore also be taken over a prolonged time. Chenodeoxycholic acid prevents the lithogenic effect of clofibrate but it cannot presently be recommended as an adjunct to clofibrate treatment since it simultaneously causes a rise in the serum concentration of LDL-cholesterol.