Influence of clofibrate, bile-sequestering agents and probucol on high-density lipoprotein levels.
The management of lipid disorders has been greatly improved by advances in our understanding of lipoprotein metabolism. New developments in the isolation and quantitation of the lipoprotein apoproteins have shed light on their essential role in normal and abnormal lipid transport and have helped clarify the mode of action of lipid-lowering drugs. Excess lipid levels can occur because of overproduction, faulty degradation or defective removal of 1 or more lipoproteins. Clofibrate appears to decrease levels of very low density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL) by enhancing their intravascular degradation. Although it often slightly decreases low-density lipoprotein (LDL) levels, it may markedly increase LDL levels in patients with initially high VLDL levels. Its effects on high-density lipoproteins (HDL) are small, often increasing HDL slightly. Bile acid sequestrants act by enhancing the rate of removal of LDL. Their effects on VLDL and IDL are slight. In some subjects there is a moderate increase in both VLDL and IDL levels. HDL concentrations are increased minimally. Probucol's mechanism of action is still unclear, but it appears to enhance LDL removal. Its effects on VLDL and IDL are minimal. Of concern is the repeated observation that probucol reduces HDL concentrations by decreasing HDL synthesis. The resultant reduction in HDL concentrations often rivals its effect in decreasing LDL levels. Knowledge of the selective effect of lipid-lowering drugs on specific lipoprotein fractions is essential for their proper therapeutic selection.
D001647:Bile Acids and Salts / Q000378:metabolism; D002994:Clofibrate; D015248:Gemfibrozil; D006801:Humans; D000960:Hypolipidemic Agents; D008074:Lipoproteins / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood*; D009539:Nicotinic Acids; D010421:Pentanoic Acids; D010636:Phenols; D011341:Probucol
D001647:Bile Acids and Salts; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D009539:Nicotinic Acids; D010421:Pentanoic Acids; D010636:Phenols; D002994:Clofibrate; D011341:Probucol; D015248:Gemfibrozil