Urien S, Riant P, Albengres E, Brioude R, Tillement J P
Mol Pharmacol. 1984 Sep;26(2):322-7.
The role of human plasma lipoproteins as carriers in the blood transport of the cholesterol-lowering and water-insoluble drug, probucol, was investigated in in vitro studies. [14C]Probucol was incubated in whole human blood, a serum pool, individual diluted sera, and isolated protein and lipoprotein fractions. In whole blood, about 90% partitioned in plasma. Following ultracentrifugal fractionation of the serum, it was found that less than 5% distributed in the d greater than 1.20 protein fraction (albumin-rich fraction) and more than 95% in the lipoprotein fractions. The distribution of probucol in the lipoprotein fractions correlated with the lipoprotein total lipid volume under saturation conditions (incubation of isolated lipoprotein fractions) as well as nonsaturation conditions (fractionation of serum exposed to [14C]probucol). Incubation of the albumin-rich fraction and of apolipoproteins originating from the isolated lipoprotein fractions showed that they account for a negligible part in the interaction of probucol with blood components. The probucol uptake of individual sera was shown to be correlated to the lipid content of the serum. When probucol was incubated in erythrocyte suspensions containing variable amounts of lipoproteins, probucol partitioned less in erythrocytes as the lipoprotein concentration increased in the suspension.
在体外研究中，对人血浆脂蛋白在降胆固醇且水不溶性药物普罗布考的血液运输中作为载体的作用进行了研究。将[14C]普罗布考与人全血、血清池、个体稀释血清以及分离的蛋白质和脂蛋白组分一起孵育。在全血中，约90%分布于血浆中。血清经超速离心分级分离后发现，小于5%分布于密度大于1.20的蛋白质组分（富含白蛋白的组分）中，而超过95%分布于脂蛋白组分中。在饱和条件下（分离的脂蛋白组分孵育）以及非饱和条件下（暴露于[14C]普罗布考的血清分级分离），普罗布考在脂蛋白组分中的分布与脂蛋白总脂体积相关。富含白蛋白的组分以及源自分离的脂蛋白组分的载脂蛋白的孵育表明，它们在普罗布考与血液成分的相互作用中所占比例可忽略不计。个体血清对普罗布考的摄取显示与血清的脂质含量相关。当普罗布考在含有不同量脂蛋白的红细胞悬液中孵育时，随着悬液中脂蛋白浓度的增加，普罗布考在红细胞中的分布减少。
