The role of the exogenous pathway in hypercholesterolaemia

The concentration of plasma cholesterol is regulated by endogenous and exogenous pathways of cholesterol metabolism. In the endogenous pathway, cholesterol is synthesized by the liver and extrahepatic tissues, and enters the circulation as a component of lipoproteins, or is secreted into bile. In the exogenous pathway, cholesterol from dietary and biliary sources is absorbed in the intestine and ultimately enters the circulation as a component of chylomicrons. A new class of drugs, the selective cholesterol absorption inhibitors, offers a different approach to current strategies available for the management of hypercholesterol-aemia. Ezetimibe, the first of these new compounds, inhibits intestinal absorption of dietary and biliary choles-terol, and lowers total cholesterol and low-density lipopro-tein cholesterol (LDL-C) levels in humans. By inhibiting cholesterol absorption, and thereby possibly reducing the cholesterol content of chylomicrons, ezetimibe may also decrease the potential atherogenicity of chylomicrons and their remnants. Combination therapy with ezetimibe and statins, which inhibit cholesterol synthesis, provides broader control of lipid levels by impacting both the exogenous and endogenous pathways of cholesterol metabolism. Such combination therapy may be a con-venient and more practical option for LDL-C reduction