Pharmacotherapy Newsletter
Volume 1, Issue 41, 10/26/2009
Question
What is the exact mechanism of action by which ezetimibe (Zetia®) actually inhibits the absorption of cholesterol in the intestine, thereby resulting in a reduction in LDL-cholesterol concentrations?
Answer
Ezetimibe (Zetia®) is the first cholesterol absorption inhibitor that can primarily reduce low density lipoprotein cholesterol (LDL-C), either as monotherapy, in combination with HMG CoA reductase inhibitor (statin) therapy, in combination with fenofibrate, or in patients with homozygous familial hypercholesterolemia on either atorvastatin or simvastatin and in patients with homozygous sitosterolemia.1-5 It has been especially useful in helping some patients with significant hyperlipidemia to get to their individualized LDL-C goals when max doses of statins have been tried.6 Ezetimibe's is able to inhibit cholesterol absorption by 54%, which contributes to the net 18-20% reductions in LDL-C seen in lipid profiles.7 It is important to note that this improvement in LDL-C is done without any compensatory increases in triglyceride concentrations, as seen with bile acid binding resins (or bile acid sequestrants such as cholestyramine, colesevelam) and without an increased risk for developing gallstones, as sometimes seen with fibrates (fenofibrate and gemfibrozil).8-10
