Ezetimibe: an update on the mechanism of action, pharmacokinetics and recent clinical trials

Elevated serum cholesterol is a known risk factor for the development of coronary artery disease. Circulating cholesterol is a product of both cholesterol absorption from the gut and cellular cholesterol production. Ezetimibe is a novel cholesterol-lowering drug that acts at the brush border of the small intestine. Recent studies have further identified the molecular target as the Niemann-Pick C1-like transporter. Ezetimibe blocks the absorption of dietary and biliary cholesterol and plant sterols resulting in intracellular cholesterol depletion. Clinical studies have demonstrated beneficial improvements in the lipid profile with ezetimibe as monotherapy, but dramatic effects are seen when ezetimibe is combined with other lipid-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Combination studies of ezetimibe with statins, bile acid sequestrants, fenofibrate and niacin all demonstrate significant total and low density lipoprotein cholesterol lowering. An excellent safety and tolerability profile combined with once-daily dosing make this attractive adjunct therapy for the treatment of hypercholesterolemia.