ADME Profiling Cambridge, Metabolism and Pharmacokinetics, Novartis Institute for Biomedical Research, 250 Mass Ave, Cambridge, MA 02139, USA.
Chem Biodivers. 2009 Nov;6(11):1887-99. doi: 10.1002/cbdv.200900117.
The drastic increase in the cost for discovering and developing a new drug along with the high attrition rate of development candidates led to shifting drug-discovery strategy to parallel assessment of comprehensive drug physicochemical, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties alongside efficacy. With the proposal of a profiling paradigm and utilization of integrated risk assessment, one can exponentially enhance the predictive power of in vitro tools by taking into consideration the interplay among profiling parameters. In particular, this article will review recent advances in accurate assessment of solubility and other physicochemical parameters. The proper interpretation of these experimental data is crucial for rapid and meaningful risk assessment and rational optimization of drug candidates in drug discovery. The impact of these tools on assisting drug-discovery teams in establishing in vitro-in vivo correlation (IVIVC) as well as structure-property relationship (SPR) will be presented.
随着发现和开发新药的成本大幅增加，以及开发候选药物的高淘汰率，药物发现策略已经转向同时评估药物的全面理化性质以及吸收、分布、代谢、排泄和毒性（ADMET）特性和疗效。随着剖析范式的提出和综合风险评估的利用，通过考虑剖析参数之间的相互作用，可以极大地提高体外工具的预测能力。特别是，本文将综述在准确评估溶解度和其他物理化学参数方面的最新进展。正确解释这些实验数据对于快速和有意义的风险评估以及合理优化药物发现中的候选药物至关重要。还将介绍这些工具在帮助药物发现团队建立体外-体内相关性（IVIVC）和结构-性质关系（SPR）方面的影响。
