应用仿生高效液相色谱法估计早期药物发现化合物的体内行为

K. Valko
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引用次数: 17

摘要

表征大量化合物的性质并估计其潜在的吸收、分布、代谢和消除性质是药物发现过程中的重要早期阶段,有助于减少后期损耗。与传统的辛醇/水分配系数相比,使用含有蛋白质和磷脂的固定相的色谱分离原理更适合于化合物表征和药代动力学性质的估计。这项技术一旦标准化,就可以预测体内行为,并选择具有最佳潜力的化合物,从而减少动物实验的数量。色谱法在未来可能会更广泛地用于测量化合物与蛋白质和受体结合的动力学方面,这将使设计需要较低剂量频率并具有更可预测的药代动力学特征的化合物成为可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Application of biomimetic HPLC to estimate in vivo behavior of early drug discovery compounds
Characterizing the properties of large numbers of compounds and estimating their potential absorption, distribution, metabolism and elimination properties are important early stages in the process of drug discovery and help to reduce later stage attrition. The chromatographic separation principles using stationary phases that contain proteins and phospholipids are more suitable for compound characterization and estimation of the pharmacokinetic properties than the traditional octanol/water partition coefficient. This technology, when standardized, enables the prediction of in vivo behavior and the selection of compounds with the best potential, thus reducing the number of animal experiments. Chromatography may be involved more widely in the future to measure kinetic aspects of compounds’ binding to proteins and receptors which would enable designing compounds that require a lower frequency of doses and have more predictable pharmacokinetic profiles.
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