Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers.
Cholesterol-lowering effect of mevinolin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a reductase, in healthy volunteers.
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Mevinolin（一种 3-羟基-3-甲基戊二酰辅酶还原酶抑制剂）对健康志愿者的降胆固醇作用。
DOI：
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发表时间：
1982
影响因子：
15.9
通讯作者：
J. Bolognese
中科院分区：
文献类型：
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作者：
J. Tobert;G. Bell;J. Birtwell;I. James;W. Kukovetz;J. Pryor;A. Buntinx;I. Holmes;Y. Chao;J. Bolognese
Mevinolin通过抑制3-羟基-3-甲基戊二酰辅酶A还原酶减少胆固醇合成。在5个中心的59名健康男性（血清胆固醇3.88- 7.76mmol/L）中进行了双盲、安慰剂对照研究，评价了该药物的安全性和有效性。受试者保持其日常饮食和活动。剂量为6.25、12.5、25或50 mg，每日2次，共4周，使血清总胆固醇平均降低23- 27%[与安慰剂（4%）相比，P <0.01]。平均低密度脂蛋白胆固醇下降35- 45%，而高密度脂蛋白和极低密度脂蛋白胆固醇，甘油三酯没有显着影响。平均载脂蛋白B下降27- 34%。50 mg并不比6.25 mg更有效。Mevinolin通常耐受良好，未发生严重的临床或实验室异常。1例受试者（12.5 mg）因腹痛和腹泻退出研究。这些结果表明，如果能够证明长期安全性，则3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂可能被证明在治疗高胆固醇血症中有用。
Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The safety and effectiveness of this agent was evaluated in a double-blind, placebo-controlled study in 59 healthy men (serum cholesterol 3.88--7.76 mmol/liter) in five centers. Subjects maintained their usual diet and activities. Doses of 6.25, 12.5, 25, or 50 mg twice daily for 4 wk produced mean reductions of total serum cholesterol fo 23--27% [vs. placebo (4%), P less than 0.01]. Mean low density lipoprotein cholesterol fell 35--45%, while high density lipoprotein and very low density lipoprotein cholesterol, and triglycerides were not significantly affected. Mean apolipoprotein B fell 27--34%. 50 mg was not significantly more effective than 6.25 mg. Mevinolin was generally well tolerated, and no serious clinical or laboratory abnormalities occurred. One subject (12.5 mg) was withdrawn because of abdominal pain and diarrhea. These results suggest that if long-term safety can be demonstrated, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia.