Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins

Abstract

Fibric acid derivatives (FADs) are a class of drugs that have been shown to reduce the production of very low-density lipoprotein (VLDL) while enhancing VLDL clearance due to the stimulation of lipoprotein lipase activity. The drugs can reduce plasma triglyceride levels while raising high-density lipoprotein (HDL) cholesterol levels. Their effects on low-density lipoprotein (LDL) cholesterol levels are less marked and more variable. There is evidence that oral gemfibrozil (Lopid, Parke-Davis, Morris Plains, NJ) can reduce the risk of serious coronary events, specifically in those patients who had elevations of both LDL cholesterol levels and total plasma triglyceride levels with lower HDL cholesterol levels. Newer FADs (bezafibrate, ciprofibrate, fenofibrate) have been shown to have greater efficacy in reducing LDL cholesterol than gemfibrozil but, in general, these drugs are not as effective as the other primary drugs used to lower LDL levels. The FADs are also used to treat adult patients with very high levels of triglycerides who have pancreatitis and whose disease cannot be managed with dietary therapy. The FADs are well tolerated, with dyspepsia and abdominal pain the most common adverse effects. A small risk of cholelithiasis exists with these drugs, and caution should be used when combining these drugs with HMG-CoA reductase inhibitors because the combination increases the incidence of hyperlipidemic myositis and rhabdomyolysis.