Bezafibrate is a known activator of peroxisome proliferator-activated receptors (PPARs) that can activate both PPARalpha and PPARbeta.
Bezafibrate causes significant reduction in plasma triglycerides and VLDL and LDL cholesterol. HDL levels are increased. Main mode of action is to increase the activity of lipoprotein lipase and several other enzymes. Increases the effects of anticoagulants in patients with hyperlipoproteinaemia. Bezafibrate lowers elevated blood lipids (triglycerides and cholesterol). Elevated VLDL and LDL are reduced by treatment with bezafibrate, whilst HDL-levels are increased. The activity of triglyceride lipases (lipoprotein lipase and hepatic lipoprotein lipase) involved in the catabolism of triglyceride-rich lipoproteins is increased by bezafibrate. In the course of the intensified degradation of triglyceride-rich lipoproteins (chylomicrons, VLDL) precursors for the formation of HDL are formed which explains an increase in HDL. Furthermore, cholesterol biosynthesis is reduced by bezafibrate, which is accompanied by a stimulation of the LDL-receptor-mediated lipoprotein catabolism.
Bezafibrate is indicated for use in patients with a fully defined and diagnosed abnormality where diet or lifestyle improvement (e.g. weight reduction, increase exercise) are insufficient to correct the condition and in whom long-term risks associated with the condition warrant treatment. The rationale for the use of bezafibrate to control abnormal elevations of serum lipids and lipoproteins is to reduce or prevent the long term adverse effects that have been shown by many epidemiological studies to be positively and strongly correlated with such hyperlipidaemias. Bezafibrate is also indicated for secondary hyperlipidaemia e.g. severe hypertriglyceridaemias, when sufficient improvement does not occur after correction of the underlying disorder (refer to Further Information) e.g. diabetes mellitus.
Due to their major action on lipoprotein and hepatic triglyceride lipase, the fibrates appear to produce a greater reduction on the VLDL than on the LDL fraction. Therapeutic doses of bezafibrate produce variable elevations of HDL cholesterol, a reduction in the content of LDL cholesterol, and a substantial reduction in the triglyceride content of the VLDL fraction. Changes by bezafibrate in the lipid components (VLDL-triglycerides, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol) are usually paralleled by changes in the corresponding apolipoproteins: apolipoprotein B is reduced, while apolipoprotein A1 and A2 may be increased.