Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal.
Trends Pharmacol Sci. 2010 Oct;31(10):449-54. doi: 10.1016/j.tips.2010.06.007. Epub 2010 Aug 19.
The affinity of a drug candidate for a biological membrane (its lipophilicity) is closely related to the pharmacologically crucial events of absorption, biodistribution, metabolization and excretion. The evolution of knowledge of biological membranes during the past two decades contrasts with the rudimentary parameter most commonly used to assess lipophilicity: P(o/w), the octanol-water partition coefficient. P(o/w) is especially unrealistic when testing molecules that are polar or partially charged. By contrast, lipid vesicle-based methods determine the extent of the actual partition of a drug to a membrane much more accurately, and have the additional advantage of enabling the choice of the lipid composition considered most suitable to answer a specific biological or pharmaceutical question. In addition, some of these methods are appropriate for high throughput screening, thus shifting determinations of membrane partition to a more preliminary stage of drug development. This streamlines research and development, by saving the time and money that would be spent on unpromising leads.
药物候选物与生物膜的亲和力（亲脂性）与其吸收、分布、代谢和排泄等药理学关键事件密切相关。在过去的二十年中，人们对生物膜的认识不断发展，而最常用于评估亲脂性的基本参数：辛醇-水分配系数（P(o/w)）却相对落后。当测试极性或部分带电的分子时，P(o/w)尤其不切实际。相比之下，基于脂质体的方法可以更准确地确定药物实际分配到膜的程度，并且具有额外的优势，可以选择被认为最适合回答特定生物学或药物问题的脂质组成。此外，这些方法中的一些适用于高通量筛选，从而将膜分配的测定转移到药物开发的更初步阶段。这通过节省在无前途的先导化合物上花费的时间和金钱，简化了研究和开发过程。
