Indications
Bezafibrate is indicated for the management of primary hyperlipidemia as classified by types IIa, IIb, III, IV, and V according to the Fredrickson classification. These correspond to groups I, II, and III of the European Atherosclerosis Society guidelines. It is recommended for patients who do not achieve adequate results through diet modifications or lifestyle improvements such as increased exercise or weight reduction. Additionally, bezafibrate is used for secondary hyperlipidemias, such as severe hypertriglyceridemia, particularly when correcting the underlying condition, such as diabetes mellitus, does not yield sufficient improvement.
Pharmacodynamics
Bezafibrate acts as an antilipemic agent, effectively lowering cholesterol and triglyceride levels. It reduces low-density lipoproteins (LDL) and enhances high-density lipoproteins (HDL). By stimulating the activity of lipoprotein lipases, particularly lipoprotein lipase and hepatic lipoprotein lipase, bezafibrate promotes the breakdown of triglyceride-rich lipoproteins, such as chylomicrons and very-low-density lipoproteins (VLDL), thus increasing HDL formation. This is complemented by a decrease in cholesterol biosynthesis and an enhancement of LDL-receptor-mediated lipoprotein catabolism. Notably, bezafibrate significantly reduces elevated plasma fibrinogen levels, which are considered a critical risk factor alongside lipids, smoking, and hypertension, contributing to atheroma development. The reduction in fibrinogen leads to decreased blood and plasma viscosity and the inhibition of platelet aggregation. Furthermore, diabetic patients have reported lowered blood glucose levels due to increased glucose tolerance, along with reduced fasting and postprandial free fatty acid concentrations.
Absorption
Bezafibrate is almost entirely absorbed upon oral administration. However, the relative bioavailability of the retard formulation of bezafibrate is approximately 70% when compared to its standard form.
Metabolism
Bezafibrate undergoes hepatic metabolism.
Mechanism of Action
Bezafibrate primarily functions as an agonist of PPAR-alpha, a role that is widely recognized and supported by existing scientific literature. In addition to its primary mechanism, some studies have indicated that bezafibrate may also exert effects on PPAR-gamma and PPAR-delta, suggesting a broader spectrum of action. This multifaceted interaction with different peroxisome proliferator-activated receptors underlines its potential in modulating lipid metabolism and associated physiological processes.
