Ezetimibe is in a new class of lipid-lowering compounds that selectively inhibit the intestinal absorption of cholesterol. Ezetimibe is orally active, and has a mechanism of action that differs from other classes of cholesterol-reducing compounds (e.g. statins, bile acid sequestrants [resins], fibric acid derivatives). The molecular target of ezetimibe is the sterol transporter, Niemann- Pick C1-Like 1 (NPC1L1), which is responsible for the intestinal uptake of cholesterol.
Ezetimibe localises at the brush border of the small intestine and inhibits the absorption of cholesterol, leading to a decrease in the delivery of intestinal cholesterol to the liver; statins reduce cholesterol synthesis in the liver and together these distinct mechanisms provide complementary cholesterol reduction. In a 2-week clinical study in 18 hypercholesterolaemic patients, ezetimibe inhibited intestinal cholesterol absorption by 54%, compared with placebo.