Ezetimibe.

Abstract

Ezetimibe, a synthetic 2-azetidinone, is the first of a new class of compounds that selectively inhibits the absorption of cholesterol and related plant sterols in the intestine. The drug, and its glucuronyl metabolite, are thought to inhibit a putative cholesterol transporter of enterocytes, located within the brush-border membrane of the small intestine. In large, randomized, placebo-controlled, 12-week trials, ezetimibe reduced levels of low density lipoprotein-cholesterol (LDL-C) by approximately 18%; triglyceride levels were reduced by approximately 6% in one trial but not another. Ezetimibe produced a modest increase in levels of high density lipoprotein-cholesterol. Moreover, reductions in LDL-C and triglyceride levels were greater in patients treated with ezetimibe coadministered with a statin (lovastatin, pravastatin, atorvastatin or simvastatin), than with either of those agents given alone. The coadministration of the lowest statin dose and ezetimibe produced similar LDL-C reductions to the administration of the highest statin dose alone. Ezetimibe also provided beneficial effects on plasma lipid levels when administered to patients with hypercholesterolemia already receiving a statin. Ezetimibe plus a statin reduced LDL-C levels more than the maximum statin dose alone in a trial in patients with homozygous familial hypercholesterolemia and was effective in a placebo-controlled trial in patients with homozygous sitosterolemia. The drug was well tolerated in clinical studies conducted to date. In large, randomized, double-blind trials, ezetimibe had a similar tolerability profile to that of placebo. Coadministration of ezetimibe and a statin did not increase the incidence of adverse events related to statin monotherapy.

• Authors: Malcolm J M Darkes, Raewyn M Poole, Karen L Goa
• Journal: American journal of cardiovascular drugs : drugs, devices, and other interventions (Am J Cardiovasc Drugs) Vol. 3 Issue 1 Pg. 67-76; discussion 77-8 ( 2003) ISSN: 1175-3277 [Print] New Zealand
• PMID: 14727947 (Publication Type: Journal Article, Review)

Chemical References

• Anticholesteremic Agents
• Azetidines
• Cholesterol, LDL
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Ezetimibe

Topics

• Animals
• Anticholesteremic Agents (pharmacology, therapeutic use)
• Azetidines (pharmacology, therapeutic use)
• Cholesterol, LDL (drug effects, metabolism)
• Clinical Trials as Topic
• Ezetimibe
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypercholesterolemia (drug therapy, metabolism)