title: 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.affiliation: Adis International Inc., Langhorne, Pennsylvania, USA.
authors.forename: Malcolm J M
authors.initials: MJ
authors.lastname: Darkes
authors.forename: Raewyn M
authors.initials: RM
authors.lastname: Poole
authors.forename: Karen L
authors.initials: KL
authors.lastname: Goa
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000187:drug effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D000069438:Ezetimibe; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069438:Ezetimibe