Ezetimibe is a member of a new class of drugs that blocks the assimilation of cholesterol from micellar particles into the enterocyte, possibly by interacting with NPC1L1, a cholesterol transport channel. Through inhibition of intestinal cholesterol absorption, ezetimibe effectively reduces the amount of biliary/dietary cholesterol delivered to the liver (via chylomicrons and chylomicron remnants) and reduces the cholesterol content of atherogenic particles (chylomicrons/chylomicron remnants, VLDL, LDL). The reduced delivery of intestinal cholesterol to the liver increases hepatic LDL receptor activity and increases clearance of circulating LDL. LDL levels are thereby reduced. Therefore, ezetimibe reduces the flux of cholesterol from the intestine to the liver.
Because this cholesterol is packaged and resecreted by the liver into the blood as VLDL particles, and because VLDL particles are the precursor particles of LDL in plasma, reduced flux of cholesterol to VLDL particles will lower LDL cholesterol. There is a compensatory response by the liver in the form of upregulation of cholesterol biosynthesis to compensate for the loss of cholesterol returning to the liver from the intestine.
Ezetimibe is the first in the class of cholesterol absorption inhibitors. It is indicated for use as monotherapy and combination therapy with statins in patients with hypercholesterolemia. Ezetimibe is contraindicated in patients with moderate or severe hepatic insufficiency.
Ezetimibe decreases the total plasma cholesterol and LDL by