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Effect of LDL-apheresis on the pharmacokinetics of the lipophilic antilipidemic agent probucol.

作者信息

Komura T, Takahara K, Sugano M, Fujinishi A, Tasaki H, Nakashima Y, Kuroiwa A

机构信息

2nd Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.

出版信息

Eur J Drug Metab Pharmacokinet. 1997 Jul-Sep;22(3):201-6. doi: 10.1007/BF03189807.

DOI:10.1007/BF03189807
PMID:9358199
Abstract

The effect of LDL-apheresis on the pharmacokinetics of antilipidemic agents has not been evaluated thoroughly. In this study, we investigated the effect of LDL-apheresis on the pharmacokinetics of probucol, a lipophilic antilipidemic agent, by studying its distribution and changes in the blood concentration of probucol after LDL-apheresis. The concentrations of lipoproteins were measured before and after LDL-apheresis in eight patients with familial hypercholesterolemia taking probucol. Concentrations of probucol in the various lipoprotein fractions and plasma were measured by HPLC. The serum concentrations of probucol before and after LDL-apheresis were 39.8 +/- 3.3 and 16.5 +/- 1.6 micrograms/ml, and the correlation coefficient between the changes in the serum probucol concentration and those in the serum cholesterol concentration before and after LDL-apheresis was significant (r = 0.73, P < 0.01). Changes in the probucol and cholesterol concentrations after LDL-apheresis were mainly found in the LDL fraction. The calculated reductions in the serum contents of probucol and cholesterol were similar to the contents of probucol and cholesterol in the irrigation fluid of the dextran sulfate column. These data suggest that changes of probucol concentration in plasma by LDL-apheresis are mainly due to reductions in the LDL fraction.

摘要

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本文引用的文献

1
Specific sorbent of apolipoprotein B-containing lipoproteins for plasmapheresis. Characterization and experimental use in hypercholesterolemic rabbits.
Arteriosclerosis. 1984 May-Jun;4(3):276-82. doi: 10.1161/01.atv.4.3.276.
2
A novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit.普罗布考降低低密度脂蛋白水平的一种新机制在低密度脂蛋白受体缺陷兔中得到证实。
J Lipid Res. 1984 Nov;25(11):1206-13.
3
In vitro studies on the distribution of probucol among human plasma lipoproteins.普罗布考在人血浆脂蛋白中分布的体外研究。
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Hypocholesterolemic effect of 4,4'-(isopropylidenedithio)-bis(2,6-di-t-butylphenol) (probucol).
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Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia.普罗布考可阻止渡边遗传性高脂血症兔(一种家族性高胆固醇血症动物模型)动脉粥样硬化的进展。
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Role of vitamin E in preventing the oxidation of low-density lipoprotein.
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Treatment of refractory familial hypercholesterolemia by low-density lipoprotein apheresis using an automated dextran sulfate cellulose adsorption system. The Liposorber Study Group.使用自动硫酸葡聚糖纤维素吸附系统进行低密度脂蛋白分离术治疗难治性家族性高胆固醇血症。脂质吸附研究组。
Am J Cardiol. 1992 Oct 15;70(11):1010-6. doi: 10.1016/0002-9149(92)90352-y.