Ezetimibe 10 mg or placebo was administered daily for a period of 12 weeks. These patients had previously been treated with lipid-lowering agents (bile acid sequestrants, nicotinic acid, fibrates, and/or statins). Ezetimibe was the major component in feces and accounted for 69% of the administered dose, while its conjugate was the major component in urine and accounted for 9% of the administered dose ( 3).ĭujovne et al performed a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of ezetimibe 10 mg in 892 patients with primary hyper-cholesterolemia. Also, multiple peaks are seen on plasma concentration-time profiles, implying enterohepatic recycling. Both forms have a long half-life of about 22 hours, accounting for their slow elimination from plasma. Both ezetimibe and its conjugate are the major drug-derived compounds detected in plasma, making up 10% to 20% and 80% to 90% of the total drug in plasma, respectively. Ezetimibe is rapidly metabolized to ezetimibe-glucuronide in humans. There has been minimal evidence of oxidative metabolism or phase I reaction in all species involved. Ezetimibe is metabolized mainly in the small intestine and liver via glucuronide conjugation, with subsequent biliary and renal excretion. Overall, ezetimibe may be taken with or without food ( 3).īoth ezetimibe and ezetimibe-glucuronide are highly bound (>90%) to human plasma proteins. However, the C max value of ezetimibe is increased by 38% when taken with a high-fat meal.

The extent of ezetimibe absorption is not affected by taking it with high-fat or nonfat meals. After a single dose, mean ezetimibe peak plasma concentrations (C max) of 3.4 to 5.5 ng/ mL were obtained within 4 to 12 hours (T max). Ezetimibe's pharmacological effect is complementary to that of the statins ( 1).Įzetimibe, which is water insoluble, is absorbed and extensively conjugated to an active phenolic glucuronide (ezetimibeglucuronide) after oral intake. It belongs to a class of lipid-lowering compounds that selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Guidelines indicating the utilization of these agents have been set by the National Cholesterol Education Program Adult Treatment Panel III ( 1).Įzetimibe (Zetia) is distinct from these agents because it does not inhibit cholesterol synthesis in the liver or increase bile acid excretion. Such drugs include hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), bile acid sequestrants, nicotinic acid, and fibric acids. For those patients who are at high risk of coronary heart disease, LDL cholesterol-lowering drug therapy may be essential. Therapeutic lifestyle changes include dietary changes, weight reduction, and increased physical activity. Modification of risk factors such as hyperlipidemia may be beneficial in slowing the atherosclerotic process and preventing cardiovascular mortality ( 1). It may be concluded that 7% of American adults are candidates for lipid-lowering agents, since dietary intervention alone reduces LDL cholesterol by only 10%. Treatment should address both diet and pharmacological therapy regimens. According to the National Health and Nutrition Examination Survey (1988–1994) and the National Cholesterol Education Program Adult Treatment Panel III, an estimated 100,870,000 American adults have total cholesterol levels ≥200 mg/dL and are at increased risk of developing coronary heart disease. Because atherosclerosis is one of the major causes of coronary heart disease, controlling plasma lipid levels is essential. Premature coronary atherosclerosis is a major manifestation of hyperlipidemia. It has been associated with elevated levels of low-density lipoprotein (LDL) cholesterol and reduced levels of high-density lipoprotein (HDL) cholesterol. Coronary heart disease is the leading cause of death in adults in the USA.

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