Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia
Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia
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DOI：
10.1056/nejmoa061189
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发表时间：
2007-01-11
影响因子：
158.5
通讯作者：
Rader, Daniel J.
中科院分区：
文献类型：
--
作者：
Cuchel, Marina;Bloedon, LeAnne T.;Rader, Daniel J.
背景：纯合子家族性高胆固醇血症患者胆固醇水平显着升高，对药物治疗反应不佳，并且过早患心血管疾病的风险非常高。抑制微粒体甘油三酯转移蛋白可能有效降低这些患者的胆固醇水平。 方法：我们进行了一项剂量递增研究，以检查 BMS-201038（一种微粒体甘油三酯转移蛋白抑制剂）在 6 名纯合子家族性高胆固醇血症患者中的安全性、耐受性及其对血脂水平的影响。治疗前4周暂停所有降脂治疗。患者接受四种不同剂量的 BMS-201038（每天每公斤体重 0.03、0.1、0.3 和 1.0 毫克），每种剂量持续 4 周，并在 4 周的药物清除期后返回进行最后一次就诊。在整个研究过程中进行了血脂水平分析、安全性实验室分析以及肝脏脂肪含量磁共振成像。 结果：所有患者都能耐受滴定至最高剂量，即每天每公斤 1.0 毫克。该剂量的治疗使低密度脂蛋白 (LDL) 胆固醇水平较基线降低 50.9%，载脂蛋白 B 水平降低 55.6%（P
BACKGROUND:Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels, which respond poorly to drug therapy, and a very high risk of premature cardiovascular disease. Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients.METHODS:We conducted a dose-escalation study to examine the safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of the microsomal triglyceride transfer protein, in six patients with homozygous familial hypercholesterolemia. All lipid-lowering therapies were suspended 4 weeks before treatment. The patients received BMS-201038 at four different doses (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body weight per day), each for 4 weeks, and returned for a final visit after a 4-week drug washout period. Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for fat content were performed throughout the study.RESULTS:All patients tolerated titration to the highest dose, 1.0 mg per kilogram per day. Treatment at this dose decreased low-density lipoprotein (LDL) cholesterol levels by 50.9% and apolipoprotein B levels by 55.6% from baseline (P