Ezetimibe: first in a new class of cholesterol absorption inhibitors

Abstract

Ezetimibe is a selective cholesterol absorption inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids. Ezetimibe reduces the small intestinal enterocyte uptake and absorption of cholesterol, which keeps the cholesterol in the intestinal lumen for excretion. Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it prevents cholesterol absorption. Enterohepatic recirculation of ezetimibe and/or its glucuronide ensures repeated delivery to the site of action and limited peripheral exposure. Ezetimibe has no effect on the activity of major drug metabolizing enzymes (CYP450), which reduces any potential drug–drug interactions with other medications. Ezetimibe (10 mg/day) was found to inhibit cholesterol absorption by an average of 54% in hypercholesterolemic individuals ( p<0.001). Ezetimibe alone reduced plasma total and LDL-C (18%) levels ( p<0.001) in patients with primary hypercholesterolemia. When ezetimibe was added to ongoing statin treatment, an additional 25% reduction in LDL-C was found in patients with primary hypercholesterolemia and an additional 21% reduction in LDL-C in homozygous familial hypercholesterolemia ( p<0.001). Ezetimibe, in combination with a statin, produces additional reductions in plasma cholesterol levels and allows for more patients to achieve their LDL-C goals.