Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia.
Hypocholesterolemic effects of mevinolin in patients with heterozygous familial hypercholesterolemia.
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美维诺林对杂合子家族性高胆固醇血症患者的低胆固醇作用。
DOI：
10.1172/jci111618
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Sexton,GJ
中科院分区：
文献类型：
--
作者：
Illingworth,DR;Sexton,GJ
我们评价了13例杂合性家族性高胆固醇血症(FH)患者应用3-羟基-3-甲基戊二酰辅酶A还原酶(胆固醇生物合成限速酶)竞争性抑制剂甲维诺林的降血脂作用。患者维持低胆固醇饮食，并按顺序递增剂量，每天服用5，10，20和40毫克的梅维诺林，每次为期1个月。每日两次服用5 mg的低密度脂蛋白胆固醇降低19.8%(与基线比较P<0.05)，每日两次服用10 mg的梅维诺林降低28.4%(P<0.05对5 mg)，每日两次服用20 mg的梅维诺林降低35%(P<0.05对10 mg)，每天服用40 mg的梅维诺林降低37.7%(与每日两次的20 mg相比无统计学差异)。服用所有剂量的梅维诺林后，高密度脂蛋白胆固醇的浓度保持稳定，而每日两次服用20毫克(-30.7%)和40毫克(-34.3%)的梅维诺林，血浆甘油三酯水平显着下降。梅维诺林耐受性良好，所有患者都完成了研究。研究期间的副作用仅限于两名患者的一过性失眠和头痛，三名患者的一过性碱性磷酸酶升高，以及第四名患者的轻度但持续的碱性磷酸酶升高。这些结果表明，梅维诺林对杂合子FH患者是一种有效的降血脂药物，但这些患者的最佳剂量比以前在正常志愿者中报道的要大。如果能够令人满意地建立长期安全性，梅维诺林在杂合子FH的治疗中提供了相当大的前景。
We have evaluated the hypolipidemic effects of mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in cholesterol biosynthesis in 13 patients with heterozygous familial hypercholesterolemia (FH). Patients were maintained on a low-cholesterol diet and received sequentially increasing doses of 5, 10, 20, and 40 mg of mevinolin twice daily for a period of 1 mo on each dose. Plasma concentrations of low density lipoprotein cholesterol decreased by 19.8% on the 5 mg twice daily dose (P less than 0.05 vs. base line), 28.4% on 10 mg of mevinolin twice daily (P less than 0.05 vs. 5 mg twice daily), 35% on 20 mg of mevinolin twice daily (P less than 0.05 vs. 10 mg twice daily), and 37.7% on 40 mg of mevinolin twice daily (not statistically different from 20 mg twice daily). Concentrations of high density lipoprotein cholesterol remained stable on all doses of mevinolin whereas plasma triglyceride levels fell significantly on the 20 mg (-30.7%) and 40 mg (-34.3%) twice daily doses of mevinolin. Mevinolin was well tolerated and all patients completed the study period. Side effects during the period of study were limited to transient insomnia and headaches in two patients, transient increases in alkaline phosphatase in three patients, and a modest but sustained increase in alkaline phosphatase in a fourth patient. These results indicate that mevinolin is an effective hypolipidemic agent in patients with heterozygous FH but that the optimal doses in these patients are greater than those previously reported in normal volunteers. If long-term safety can be satisfactorily established, mevinolin offers considerable promise in the therapy of heterozygous FH.
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DOI：
--
发表时间：
1962
期刊：
Journal of Physiology
影响因子：
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作者：
J. Diamond
通讯作者：
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影响因子：
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影响因子：
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作者：
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作者：
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影响因子：
15.9
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R. T. Whitlock;H. O. Wheeler
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