Lin Jing, Sahakian Diana C, de Morais Sonia M F, Xu Jinghai J, Polzer Robert J, Winter Steven M
Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Groton Laboratories, CT 06340, USA.
Curr Top Med Chem. 2003;3(10):1125-54. doi: 10.2174/1568026033452096.
Major reasons preventing many early candidates reaching market are the inappropriate ADME (absorption, distribution, metabolism and excretion) properties and drug-induced toxicity. From a commercial perspective, it is desirable that poorly behaved compounds are removed early in the discovery phase rather than during the more costly drug development phases. As a consequence, over the past decade, ADME and toxicity (ADMET) screening studies have been incorporated earlier in the drug discovery phase. The intent of this review is to introduce the desirable attributes of a new chemical entity (NCE) to the medicinal chemist from an ADMET perspective. Fundamental concepts, key tools, reagents and experimental approaches used by the drug metabolism scientist to aid a modern project team in predicting human pharmacokinetics and assessing the "drug-like" molecule are discussed.
阻碍许多早期候选药物进入市场的主要原因是其不合适的药代动力学（吸收、分布、代谢和排泄）特性以及药物诱导的毒性。从商业角度来看，理想的情况是在发现阶段早期就淘汰表现不佳的化合物，而不是在成本更高的药物开发阶段。因此，在过去十年中，药代动力学和毒性（ADMET）筛选研究已被更早地纳入药物发现阶段。本综述的目的是从ADMET角度向药物化学家介绍新化学实体（NCE）的理想属性。讨论了药物代谢科学家用于帮助现代项目团队预测人体药代动力学和评估“类药物”分子的基本概念、关键工具、试剂和实验方法。
