Ezetimibe: an update on the mechanism of action, pharmacokinetics and recent clinical trials

Abstract

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.

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

“…The constant value depended on the specific type of medications used (Supplementary Materials, Table S2) (32)(33)(34). If multiple medications were used, we applied the correction factor with the largest effect (e.g.…”

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome

“…5 Ezetimibe, an inhibitor of intestinal cholesterol absorption, significantly lowers LDL-C, modestly decreases triglycerides (TG), and raises HDL-C levels. 6 When combined with simvastatin, the two drugs provide complementary improvements in the atherogenic lipid profile of patients with hyperlipidaemia. 7,8 Rosuvastatin represents the most potent statin currently available in terms of both the lower statin dosage and LDL-C lowering.…”

Five-Year Follow-up after Laparoscopic Roux-en-Y Gastric and Partial Ileal Bypass for Treatment of Morbid Obesity and Uncontrolled Hyperlipidemia

“…PIB has fallen out of favor due to the effectiveness of statin-based medical therapy for hyperlipidemia and the arrival of new medications that affect the cholesterol pathway [13,14,15]. In addition, the potential side effects of PIB include diarrhea, kidney stones, gallstones, gas bloat syndrome, and bowel obstruction attributable to postoperative adhesion formation [6].…”