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The role of the exogenous pathway in hypercholesterolaemia

J. Shepherd*

Royal Infirmary, Glasgow, Scotland, U.K.

* Correspondence: Professor James Shepherd, MB, ChB, PhD, Department of Pathological Biochemistry, University of Glasgow, and Royal Infirmary, 84 Castle Street, Glasgow, Scotland G4 0SF, U.K.

Abstract

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 hypercholesterolaemia. Ezetimibe, the first of these new compounds, inhibits intestinal absorption of dietary and biliary cholesterol, and lowers total cholesterol and low-density lipoprotein 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 convenient and more practical option for LDL-C reduction.

Key Words: Exogenous cholesterol pathway • hypercholesterolaemia • cholesterol metabolism • cholesterol absorption inhibition • ezetimibe • statins


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Home page
 The Annals of PharmacotherapyHome page
V. F Mauro and C. E Tuckerman
Ezetimibe for Management of Hypercholesterolemia
Ann. Pharmacother., June 1, 2003; 37(6): 839 - 848.
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