|
|
 |
|
|
| TWO SOURCES OF CHOLESTEROL / DUAL INHIBITION |
|
- There are two main sources of cholesterol, which are similar in size: production of cholesterol, mainly from the liver, and absorption of cholesterol in the intestine.1-3
- Approximately 50% of the intestinal cholesterol is absorbed and re-circulated through the intestine. The rest of the intestinal cholesterol is excreted in the feces.2
- The intestinal pool is composed of both excreted biliary cholesterol (the majority) and dietary cholesterol.1
- Both sources, production in the liver and absorption in the intestine, are important.
|
|
|
|
|
|
| DUAL INHIBITION TO CONTROL SOURCES OF CHOLESTEROL 4, 5 |
 |
|
*Total daily intestinal cholesterol equals 50% from hepatic secretions, 30% from dietary sources, and 20% from sloughing of epithelial cells.
Adapted from van Heek M et al Br J Pharmacol 2000;129:1748-1754;
Shepard J Eur Heart J Suppl 2001;3(suppl E): E2-E5;Bays H Expert Opin Investig Drugs 2002;11:1587-1604. |
|
|
|
- EZETROL selectively inhibits cholesterol absorption in the intestine, while statins inhibit cholesterol synthesis in the liver.4
- The Dual Inhibition of these two sources of cholesterol by EZETROL co-administered with a statin is complementary, and significantly more effective in reducing the overall cholesterol level than inhibiting only one of the sources (p<0.01)2,6-9
|
|
|
|
|
|
| FIRST IN A NEW CLASS 2,4 |
|
- EZETROL, a cholesterol absorption inhibitor, is the first in a new class of lipid-lowering compounds that selectively inhibit the intestinal absorption of cholesterol.2,4
- EZETROL has a mechanism of action different from other lipid-lowering agents (statins, bile-acid sequestrants [resins], and fibrates).2,4
Cholesterol Absorption
- Dietary and biliary cholesterol in the lumen of the small intestine is packaged into micelles that diffuse across a thin mucus layer to the surface of the intestinal epithelial cells (enterocytes).3,10 Upon reaching the enterocyte, cholesterol is released from the micelle.3 The cholesterol then passes through the mucosal membrane of the enterocyte by a mechanism that is thought to be mediated by a transporter within the brush border.11
- Soon after administration, the majority of ezetimibe and the active metabolite localizes in the enterocyte brush border, with the remainder passing through the portal circulation and returned to the intestines via the bile.5,12 The localization of ezetimibe in the brush border is thought to inhibit the cholesterol transport mechanism, thus preventing biliary and dietary cholesterol from entering the bloodstream. Consequently, less cholesterol is delivered to the liver, which causes a reduction of hepatic cholesterol stores and increases clearance of cholesterol from the blood.5
- Additionally, EZETROL does not affect the absorption of fat-soluble vitamins.4
|
|
|
|
|
|
|
|
|
Play Video
