Shireman R B, Remsen J F
Life Sci. 1983 Nov 28;33(22):2165-71. doi: 10.1016/0024-3205(83)90287-4.
It has been proposed that in vivo variability in response to certain hydrophobic chemicals or drugs, such as imipramine, may be due in part to the varying plasma lipid levels in patients. The distribution of [3H]imipramine into the lipoproteins of human plasma was therefore studied. Differential density centrifugation of plasma containing [3H]imipramine resulted in flotation of very low density, low density and high density lipoproteins (VLDL, LDL, HDL) and approximately one-third of the total 3H radioactivity. Twelve percent of the radioactivity was present in the sedimented fraction which included most of the plasma proteins. There appeared to be little specific binding of [3H]imipramine to VLDL or LDL, as shown by ultracentrifugation, dialysis and column chromatography. [3H]Imipramine was readily incorporated into cultured human fibroblasts;o no differences were observed in cellular uptake whether it was added to the medium in plasma, LDL or HDL. Also, no differences in uptake of [3H]imipramine by LDL-receptor positive and receptor negative cells were noted. These experiments indicate that LDL is not a major vehicle for the transport of this drug and that both the bound and free fractions are available for cellular uptake.
有人提出，患者对某些疏水化学物质或药物（如丙咪嗪）的体内反应变异性，可能部分归因于患者血浆脂质水平的变化。因此，研究了[3H]丙咪嗪在人血浆脂蛋白中的分布。对含有[3H]丙咪嗪的血浆进行差速密度离心，导致极低密度脂蛋白、低密度脂蛋白和高密度脂蛋白（VLDL、LDL、HDL）漂浮，约占总3H放射性的三分之一。12%的放射性存在于沉淀部分，其中包括大部分血浆蛋白。超速离心、透析和柱色谱显示，[3H]丙咪嗪与VLDL或LDL似乎几乎没有特异性结合。[3H]丙咪嗪很容易掺入培养的人成纤维细胞中；无论将其添加到血浆、LDL或HDL中的培养基中，细胞摄取均未观察到差异。此外，LDL受体阳性和受体阴性细胞对[3H]丙咪嗪的摄取也没有差异。这些实验表明，LDL不是这种药物运输的主要载体，结合部分和游离部分均可用于细胞摄取。
