Barton P, Davis A M, McCarthy D J, Webborn P J
Department of Physical and Metabolic Sciences, Astra Chamwood, Loughborough, Leicestershire, United Kingdom.
J Pharm Sci. 1997 Sep;86(9):1034-9. doi: 10.1021/js960430g.
The in vivo tissue distribution of seventeen drugs has been modeled by using estimated n-octanol/water and membrane/water distribution coefficients. In this study, the membrane affinities are estimated using the new technique of immobilized artificial membrane (IAM) column chromatography. delta (log D(n-octanol/water-membrane/water)), which measures a hypothetical equilibrium of the drug between of n-octanol and membrane phase, is a better model of in vivo tissue distribution, as measured by Adipose Tissue Storage Index (ASI), than either n-octanol/ water or membrane/water distribution coefficients alone. This demonstrates the importance of membrane distribution coefficients as a complementary descriptor of lipophilicity to n-octanol/water distribution coefficients, in modeling in vivo distribution of drugs. This rapid method for predicting in vivo distribution of drugs, based on n-octanol and membrane/water distribution coefficients, may be a useful tool to aid the selection of drugs with beneficial pharmacokinetic profiles.
通过使用估计的正辛醇/水和膜/水分配系数，对17种药物的体内组织分布进行了建模。在本研究中，使用固定化人工膜（IAM）柱色谱新技术来估计膜亲和力。δ（log D（正辛醇/水-膜/水））衡量药物在正辛醇和膜相之间的假设平衡，与单独的正辛醇/水或膜/水分配系数相比，它是通过脂肪组织储存指数（ASI）衡量的更好的体内组织分布模型。这证明了膜分配系数作为对正辛醇/水分配系数亲脂性的补充描述符在药物体内分布建模中的重要性。这种基于正辛醇和膜/水分配系数预测药物体内分布的快速方法，可能是帮助选择具有有益药代动力学特征药物的有用工具。
