Audus K L, Knaub S R, Guillot F L, Schaeffer J M
Department of Pharmaceutical Chemistry, University of Kansas, School of Pharmacy, Lawrence 66045.
Vet Res Commun. 1992;16(5):365-77. doi: 10.1007/BF01839186.
The effect of albumin binding on ivermectin uptake and transfer across the endothelial component of the blood-brain barrier (BBB) was determined with an in vitro model comprised of bovine brain microvessel endothelial cell (BMEC) monolayers. Cellular uptake of ivermectin was limited in the absence of albumin and 90% inhibited in the presence of 10% albumin. Cell membrane association of ivermectin, as followed by fluorescent probe labelling, was observed only at high (micromolar) concentrations of the drug. Membrane association was about 75% inhibited in the presence of albumin. Similarly, transfer across BMEC monolayers was restricted, equivalent to that of BBB impermeant markers. Unlike the uptake studies, however, albumin had little effect on the transfer of ivermectin across BMEC monolayers. These results support recent in vivo findings on the distribution of ivermectin into the brain and suggest that ivermectin has only a limited affinity for the endothelial component of the normal BBB.
利用由牛脑微血管内皮细胞（BMEC）单层组成的体外模型，确定了白蛋白结合对伊维菌素摄取以及跨血脑屏障（BBB）内皮成分转运的影响。在无白蛋白的情况下，伊维菌素的细胞摄取受限，而在存在10%白蛋白时，摄取受到90%的抑制。仅在高（微摩尔）浓度的药物作用下，通过荧光探针标记观察到伊维菌素与细胞膜的结合。在存在白蛋白的情况下，膜结合受到约75%的抑制。同样，跨BMEC单层的转运受到限制，等同于BBB不透性标记物的转运。然而，与摄取研究不同的是，白蛋白对伊维菌素跨BMEC单层的转运影响很小。这些结果支持了最近关于伊维菌素在脑内分布的体内研究结果，并表明伊维菌素对正常BBB的内皮成分亲和力有限。
