[How does fenofibrate exert its cholesterol-lowering effect? (author's transl)]

Abstract

In animal models and in man the lipid-lowering activity of fenofibrate is characterized by a reduction of the serum fraction that carries most of the circulating cholesterol. Pharmacological studies in rodents have shown that fenofibrate induces a "catabolic" state with decreased HDL-cholesterol in normal rats and decreased VLDL-cholesterol ester and liver cholesterol ester in hypercholesterolaemic rats. The mechanism of this enhanced elimination is still unknown. The relative increase in free cholesterol in relation to cholesterol ester might indirectly reduce HMG-CoA reductase activity. In addition, we have shown a direct inhibitory effect of fenofibrate on human liver microsomic enzyme activity in vitro. The blood levels of fenofibric acid in man would be sufficient to inhibit this enzyme in vivo.