Davis Harry R, Veltri Enrico P
Department of Cardiovascular/Metabolic Disease Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
J Atheroscler Thromb. 2007 Jun;14(3):99-108. doi: 10.5551/jat.14.99.
Zetia (ezetimibe) is a selective cholesterol absorption inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids. Ezetimibe reduces the small intestinal enterocyte uptake and absorption of cholesterol by binding to Niemann-Pick C1 Like 1 (NPC1L1), which keeps cholesterol in the intestinal lumen for excretion. Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it binds with higher affinity for NPC1L1 than ezetimibe to prevent cholesterol absorption. Enterohepatic recirculation of ezetimibe and/or its glucuronide ensures repeated delivery to the intestinal site of action and limited peripheral exposure. Ezetimibe has no effect on the activity of major drug metabolizing enzymes (CYP450), which reduces any potential drug-drug interactions with other medications. Ezetimibe (10 mg/day) was found to inhibit cholesterol absorption by an average of 54% in hypercholesterolemic individuals and by 58% in vegetarians. Ezetimibe alone reduced plasma total and LDL-Cholesterol (18%) levels in patients with primary hypercholesterolemia. When ezetimibe was added to on-going statin treatment, an additional 25% reduction in LDL-C was found in patients with primary hypercholesterolemia and an additional 21% reduction in LDL-C in homozygous familial hypercholesterolemia. Ezetimibe in combination with statins produces additional reductions in plasma cholesterol levels and allows for more patients to achieve their LDL-C goals.
择捷美（依折麦布）是一种选择性胆固醇吸收抑制剂，它能有效抑制小肠对胆汁和膳食胆固醇的吸收，而不影响脂溶性维生素、甘油三酯或胆汁酸的吸收。依折麦布通过与尼曼-匹克C1样1蛋白（NPC1L1）结合，减少小肠肠上皮细胞对胆固醇的摄取和吸收，从而使胆固醇留在肠腔内以便排出。依折麦布经葡萄糖醛酸化形成单一代谢产物，并定位于肠壁，在那里它与NPC1L1的结合亲和力高于依折麦布，以防止胆固醇吸收。依折麦布及其葡萄糖醛酸化物的肠肝循环确保了药物反复输送到肠道作用部位，并限制了外周暴露。依折麦布对主要药物代谢酶（CYP450）的活性没有影响，这减少了与其他药物发生潜在药物相互作用的可能性。在高胆固醇血症患者中，发现依折麦布（10毫克/天）平均可抑制胆固醇吸收54%，在素食者中可抑制58%。单独使用依折麦布可使原发性高胆固醇血症患者的血浆总胆固醇和低密度脂蛋白胆固醇（LDL-C）水平降低18%。当将依折麦布添加到正在进行的他汀类药物治疗中时，原发性高胆固醇血症患者的LDL-C水平又降低了25%，纯合子家族性高胆固醇血症患者的LDL-C水平又降低了21%。依折麦布与他汀类药物联合使用可进一步降低血浆胆固醇水平，使更多患者达到其LDL-C目标。
