利非布罗：一种用于治疗高胆固醇血症的新型降脂药物。利非布罗研究组

Lifibrol: a novel lipid-lowering drug for the therapy of hypercholesterolemia. Lifibrol Study Group.

作者信息

Locker P K, Jungbluth G L, Francom S F, Hughes G S

机构信息

Upjohn Company, Kalamazoo, MI 49001.

出版信息

Clin Pharmacol Ther. 1995 Jan;57(1):73-88. doi: 10.1016/0009-9236(95)90269-4.

DOI:10.1016/0009-9236(95)90269-4

PMID:7828385

Abstract

OBJECTIVE

To determine the effects of lifibrol on serum lipids in adult patients with primary hypercholesterolemia.

METHODS

These were two double-blind, randomized placebo-controlled studies. Each patient in each study had an 8-week dietary lead-in period on the American Heart Association Step I diet before administration of lifibrol or placebo. The first study consisted of active dosing of 4 weeks, and the second study had 12 weeks of active dosing. The setting for the study involved outpatients in private or university hospitals in the United States. All patients had primary hypercholesterolemia with low-density lipoprotein (LDL) cholesterol levels of > 160 mg/dl after the dietary lead-in period. There were 155 patients in the 4-week study and 336 patients in the 12-week study. In the first study, patients were randomly assigned to receive either 150, 300, 450, 600, or 900 mg lifibrol as a single daily dose for 4 weeks. In the second study, patients were randomized to receive either 150, 300, or 600 mg lifibrol for 12 weeks. Efficacy was determined by serial measurements of serum lipids either on a weekly or biweekly basis during each study.

RESULTS

Compared with baseline, lifibrol reduced LDL cholesterol (> 40%, p < 0.0001) and apolipoprotein B (approximately 40%, p < 0.0001) by 4 weeks in both studies. After 6 weeks, high-density lipoprotein (HDL) cholesterol levels increased in the placebo and 150 and 300 mg lifibrol groups. In the 600 mg lifibrol group, triglycerides (approximately 25%, p < 0.001), lipoprotein (a) (approximately 30%, p < 0.001), and HDL cholesterol (approximately 5%, p < 0.002) decreased. Lifibrol reduced key sterol intermediates (e.g., lanosterol, lathosterol, beta-sitosterol, and campesterol) and increased serum bile acids, but it had no effect on urinary mevalonic acid excretion. The pharmacokinetics of lifibrol are independent of dose and are similar in men and women. Lifibrol was well tolerated. The most frequent medical event in both studies was skin rash.

CONCLUSIONS

Lifibrol is a potent lipid-lowering drug in patients with hypercholesterolemia.

摘要

目的

确定利非布罗对成年原发性高胆固醇血症患者血脂的影响。

方法

这是两项双盲、随机、安慰剂对照研究。每项研究中的每位患者在服用利非布罗或安慰剂之前，先按照美国心脏协会第一步饮食方案进行为期8周的饮食导入期。第一项研究包括4周的活性药物给药期，第二项研究有12周的活性药物给药期。研究地点涉及美国私立或大学医院的门诊患者。所有患者在饮食导入期后均患有原发性高胆固醇血症，低密度脂蛋白（LDL）胆固醇水平>160mg/dl。4周研究中有155名患者，12周研究中有336名患者。在第一项研究中，患者被随机分配接受150、300、450、600或900mg利非布罗作为每日单剂量，持续4周。在第二项研究中，患者被随机分配接受150、300或600mg利非布罗，持续12周。在每项研究期间，通过每周或每两周对血脂进行系列测量来确定疗效。

结果

与基线相比，在两项研究中，利非布罗在4周时使LDL胆固醇降低（>40%，p<0.0001）和载脂蛋白B降低（约40%，p<0.0001）。6周后，安慰剂组以及150mg和300mg利非布罗组的高密度脂蛋白（HDL）胆固醇水平升高。在600mg利非布罗组中，甘油三酯（约25%，p<0.001）、脂蛋白（a）（约30%，p<0.001）和HDL胆固醇（约5%，p<0.002）降低。利非布罗降低了关键的甾醇中间体（如羊毛甾醇、麦角甾醇、β-谷甾醇和菜油甾醇）并增加了血清胆汁酸，但对尿中甲羟戊酸排泄没有影响。利非布罗的药代动力学与剂量无关，在男性和女性中相似。利非布罗耐受性良好。两项研究中最常见的医学事件是皮疹。