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.
Sweeney
Mary Ellen
ME
Emory University School of Medicine, Division of Endocrinology, Metabolism and Lipids, Atlanta VA Medical Center-111, 1670 Clairmont Rd, Atlanta, GA 30033, USA. msweene@emory.edu
Johnson
Rebecca R
RR
D000924:Anticholesteremic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001384:Azetidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D015394:Molecular Structure; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D001384:Azetidines; D002784:Cholesterol; D000069438:Ezetimibe