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The concentration of plasma cholesterol is regulated by cholesterol absorption, and thereby possibly reducing the
endogenous and exogenous pathways of cholesterol cholesterol content of chylomicrons, ezetimibe may also
metabolism. In the endogenous pathway, cholesterol is decrease the potential atherogenicity of chylomicrons and
synthesized by the liver and extrahepatic tissues, and enters their remnants. Combination therapy with ezetimibe and
the circulation as a component of lipoproteins, or is statins, which inhibit cholesterol synthesis, provides
secreted into bile. In the exogenous pathway, cholesterol broader control of lipid levels by impacting both the
from dietary and biliary sources is absorbed in the intestine exogenous and endogenous pathways of cholesterol
and ultimately enters the circulation as a component of metabolism. Such combination therapy may be a con-
chylomicrons. A new class of drugs, the selective cholesterol venient and more practical option for LDL-C reduction.
absorption inhibitors, offers a different approach to current (Eur Heart J Supplements 2001; 3 (Suppl E): E2–E5)
strategies available for the management of hypercholesterol- ? 2001 The European Society of Cardiology
aemia. Ezetimibe, the first of these new compounds,
inhibits intestinal absorption of dietary and biliary choles- Key Words: Exogenous cholesterol pathway, hypercholes-
terol, and lowers total cholesterol and low-density lipopro- terolaemia, cholesterol metabolism, cholesterol absorption
tein cholesterol (LDL-C) levels in humans. By inhibiting inhibition, ezetimibe, statins.
Endogenous BILIARY
INTESTINAL TRACT
Other LUMEN
HDL
tissues Plaque
Bile acids CE formation
Synthesis
VLDL IDL LDL Free Remnants
cholesterol
DIET Unstirred
LDL-R water
Cholesterol
layer
BLOOD
FC biosynthesis
Cholesteryl
Remnants FC ester (CE)
CE
Micelles ACAT
Biliary
cholesterol Chylomicrons Chylomicrons
LYMPH
LDL Statins
VLDL Synthesis
BILIARY
LDL-R SECRETION Absorption
Cholesterol Fecal
10 mg . day "1 (n=12) or ezetimibe 10 mg . day "1 reductase inhibitor. Arterioscler Thromb Vasc Biol 1995; 15:
(n=46) had statistically significant (P<0·01 vs placebo) 678–82.
[9] Illingworth DR. Management of hypercholesterolemia. Med
reductions in LDL-C levels from baseline (35% and Clin North Am 2000; 84: 23–42.
19%, respectively). However, patients given the combi- [10] Knopp RH. Drug treatment of lipid disorders. N Engl J Med
nation of 10 mg of simvastatin and 10 mg of ezetimibe 1999; 341: 498–511.
(n=11) achieved a reduction of 52% in LDL-C levels, [11] Lennernäs H, Fager G. Pharmacodynamics and pharmaco-
which was an additional 17% reduction beyond that kinetics of HMG-CoA reductase inhibitors: similarities and
differences. Clin Pharmacokinet 1997; 32: 403–25.
achieved with simvastatin (10 mg) monotherapy. The [12] Dujovne CA, Chremos AN, Pool JL et al. Expanded