Effects of Bezafibrate—A Hypolipidemic Drug

Abstract

Coronary heart disease is a major cause of death in industrialized countries. Substantial epidemiological evidence suggests that elevated lipid levels are associated with atherosclerotic vascular disease, and in particular, with coronary heart disease (16,84). This applies to serum cholesterol but triglyceride levels may also be of importance. A raised level of low density lipoprotein (LDL) cholesterol indicates a particular risk; conversely, the level of high density lipoprotein (HDL) cholesterol represents a protective factor.In order to prevent premature atherosclerosis, treatment with hypolipidemic drugs is frequently initiated in patients with primary hyperlipoproteinemia who do not respond adequately to dietary recommendations (68). Among such drugs, clofibrate and its analogues have been widely used for many years in patients with hyperlipoproteinemia (27,35). Bezafibrate, one of the newer derivatives of clofibrate, is a well-tolerated drug with potent hypolipidemic properties (49). To date, the effect of bezafibrate on mortality from cardiovascular disease has not yet been reported.In this review the toxicology, pharmacokinetics, mechanisms of action, and clinical effects of bezafibrate are summarized based on published data. CHEMICAL STRUCTURE AND PROPERTIESBezafibrate, 2{4-[2-(4-chlorobenzamido)ethyl)phenoxy}-2-methyl-propionic acid (Fig. 1), is structurally related to clofibrate and other fibric acid derivatives. The compound has a molecular weight of 361.5. It is a white odorless crystalline powder. In the form of the alkaline salt it is moderately soluble in water and it is easily soluble in organic solvents (e.g., ethanol and chloroform). TOXICOLOGYThe acute toxicity of bezafibrate has been studied in the rat and mouse. LD,, after intraperitoneal administration was approximately 500 mg/kg in these species; after oral administration the LD,, was approximately 2 100-2500 mgkg (29).

Soluble-fibre concentrate lowers plasminogen activator inhibitor-1 in baboons (Papio ursinus)

“…Compared with the 10 mgkg body weight perd administered intragastrically by Stegmeier et al (1980) to normolipidaemic non-human primates, the dose in our study might have been too small to lower TAG. A significant dose-response relationship for plasma cholesterol and TAG concentrations has been reported for BF (Stahlberg, 1992).…”

“…BF is an effective lipid-lowering agent in human subjects as well as in animal models (Stahlberg, 1992). The recommended dosage of the sustained formulation is 400 mg/d (6.7 mgkg for an adult weighing 60 kg).…”

“…Among such drugs, fibrates have been widely used for many years. Bezafibrate (BF), one of the new derivatives of clofibrate, is a well-tolerated drug with effective hypolipidaemic properties and has the ability to lower raised plasma fibrinogen (Stahlberg, 1992). Fibrate treatment reduces PAI-1 levels in hypertriacylgl ycerolaemic patients in whom triac ylglycerol (TAG) levels are normalized (Keber et al 1994).…”

Cardiovascular Drugs

“…They increase the rate of VLDL catabolism by stimulating lipoprotein lipase activity and/or hepatic lipase activity [57], thereby lowering mainly plasma triglycerides. Other effects are inhibition of cholesterol synthesis and increase in excretion of neutral sterols [58].…”