论文部分内容阅读
目的;预测肺泡巨噬细胞单层的体外摄取.方法:以培养的肺泡巨噬细胞单层为体外模型,用磷脂膜色谱,脂质体/水系统评价药物与磷脂膜的相互作用,分别表示为lg k_(1AM),lg D_(L B,7.4),用正辛醇/水系统测定参考的疏水性参数(lg D_(O/B,7.4).结果:lg D_(L B,7.4)(r~2=0.93)比lg D_(O B,7.4)(r~2=0.65)具有与lg k_(1AM)更显著的相关性.lg k_(1AM)和lg D_(L B,7.4)均 比lg D_(O/B,7.4)与细胞内药物的蓄积度有更好的相关性.但对于由5个两性喹酮抗生素和奎尼丁组成的受试集合,三者均与药物进入细胞内的速度具有相近的显著的正相关性.结论:磷脂膜色谱和脂质体/水系统给出相似的亲脂性测量尺度,且均与正辛醇/水系统区别有显著性.与疏水性参数相比,膜亲和性是更有效的肺泡巨噬细胞内药物蓄积和结合的预测参数.
Objective: To predict the in vitro uptake of monolayers of alveolar macrophages.Methods: The cultured alveolar macrophages monolayer was used as an in vitro model to evaluate the interaction between drug and phospholipid membrane by phospholipid membrane chromatography and liposome / water system, respectively The reference hydrophobic parameter (lg D_ (O / B, 7.4)) was determined using n-octanol / water system for lg k_ (1AM) and lg D_ (LB, (1AM) and lg D_ (LB, 7.4) were higher than that of lg D_ (2, 0.93) (O / B, 7.4) had a better correlation with the accumulation of intracellular drugs, but for the test set consisting of 5 amphetamine antibiotics and quinidine, all three were related to the rate of drug entry into the cell With similar significant positive correlation.Conclusion: Phospholipid membrane chromatography and liposome / water system give similar lipophilicity measurement scale, and have a significant difference with the n-octanol / water system.Compared with the hydrophobic parameters , Membrane affinity is a more predictive parameter for drug accumulation and binding in alveolar macrophages.