Rizzo Manfredi
University of Palermo, Department of Internal Medicine and Emerging Diseases, Via del Vespro 141, 90127 Palermo, Italy.
IDrugs. 2010 Feb;13(2):103-11.
New lipid-lowering agents include microsomal triglyceride transfer protein (MTP) inhibitors, which may have a role in the treatment of hypercholesterolemia. Clinical applications of MTP inhibitors have been focused primarily on high-dose monotherapy to produce substantial reductions in LDL-cholesterol levels (particularly for patients with homozygous familial hypercholesterolemia). However, this strategy has been associated with a high rate and severity of gastrointestinal and hepatic adverse events that has prohibited the use of these agents. Data suggest the LDL-cholesterol-lowering efficacy of low-dose lomitapide (AEGR-733, formerly BMS-201038), under development by Aegerion Pharmaceuticals Inc, in patients with familial hypercholesterolemia, both as a single agent and in combination with commonly prescribed lipid-lowering therapies. MTP inhibition with lomitapide may offer a treatment option for patients who cannot tolerate statin therapy or who experience insufficient LDL-cholesterol reduction with available therapies. However, the safety concerns for MTP inhibitors for the treatment of hyperlipidemia must be fully addressed, and the assessment of the risk-to-benefit ratio for MTP inhibitors in patients at different levels of cardiovascular-disease risk is required before clinical use of this class of drugs may be recommended.
新型降脂药物包括微粒体甘油三酯转运蛋白（MTP）抑制剂，其在高胆固醇血症的治疗中可能发挥作用。MTP抑制剂的临床应用主要集中在高剂量单药治疗，以大幅降低低密度脂蛋白胆固醇（LDL-C）水平（特别是对于纯合子家族性高胆固醇血症患者）。然而，这种策略与胃肠道和肝脏不良事件的高发生率及严重程度相关，这限制了这些药物的使用。数据表明，Aegerion制药公司正在研发的低剂量洛美他派（AEGR-733，原BMS-201038）对家族性高胆固醇血症患者具有降低LDL-C的疗效，可作为单一药物或与常用的降脂疗法联合使用。对于无法耐受他汀类治疗或现有疗法降低LDL-C效果不佳的患者，洛美他派抑制MTP可能提供一种治疗选择。然而，必须充分解决MTP抑制剂治疗高脂血症的安全性问题，在推荐临床使用这类药物之前，需要评估不同心血管疾病风险水平患者使用MTP抑制剂的风险效益比。
