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

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Abstract
To determine whether the clofibrate-induced increase in bile cholesterol saturation is transitory, duodenal bile samples were analyzed from 16 hyperlipoproteinemic patients before and after 6 mo. to 2 yr treatment with clofibrate, 2 g daily. Standardized dietary and weight conditions were obtained. In all but 2 subjects cholesterol saturation remained elevated (150 .+-. 7% mean .+-. SEM [SE of mean]) compared to pretreatment values (112 .+-. 6%, P < 0.01). In 9 of the patients, duodenal bile was obtained after 6 wk of treatment. Although 2 patients with increased saturation at 6 wk displayed a return to basal values at 2 yr, the majority showed no consistent changes between the 2 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 8 out of 9 patients studied. The serum levels of total cholesterol and triglycerides, very low density lipoprotein and high density lipoprotein cholesterol were not significantly changed. 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). Clofibrate induces changes in biliary lipid composition, which are consistent over at least 2 yr of treatment. Possible measures to avoid these effects must 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 as it simultaneously increases the serum concentration of LDL-cholesterol.