Metabolism and other pharmacokinetic (PK) studies have always played a critical role in helping to optimize the bioavailability and duration of action of new drugs thereby increasing their success rate. With the advent of automated combinatorial synthesis, high-throughput pharmacological testing, and the ability to create extensive databases in the past decade, drug discovery has undergone an amazing evolution. With the increased throughput of drug discovery, metabolism and other PK studies have evolved to keep pace. Often called "early ADME" studies, these studies are characterized by parallel processing and higher throughput than before. This article focuses on a particular class of early ADME (absorption, distribution mechanism, and excretion) studies known as "metabolic stability" studies. The theoretical basis for metabolic stability and its relationship to the concept of metabolic intrinsic clearance is briefly presented. Some key relationships between structure and metabolism are summarized. Several case studies from recent medicinal chemistry literature are reviewed to exemplify how metabolic stability studies influenced drug design and led to improvements in bioavailability and half-life. Finally, future trends in drug metabolism and analytical chemistry and how they may influence metabolic stability studies are reviewed.

中文翻译：

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优化代谢稳定性是现代药物设计的目标。

代谢和其他药代动力学（PK）研究一直在帮助优化新药的生物利用度和作用时间，从而提高其成功率方面发挥着关键作用。在过去的十年中，随着自动组合合成，高通量药理学测试和创建广泛数据库的能力的出现，药物发现经历了惊人的发展。随着药物发现通量的增加，新陈代谢和其他PK研究也不断发展。这些研究通常称为“早期ADME”研究，其特征在于并行处理和更高的吞吐量。本文着重于一类早期的ADME（吸收，分布机制和排泄）研究，称为“代谢稳定性”研究。简要介绍了代谢稳定性的理论基础及其与代谢内在清除概念的关系。总结了结构与代谢之间的一些关键关系。回顾了近期药物化学文献中的一些案例研究，以例证代谢稳定性研究如何影响药物设计并改善生物利用度和半衰期。最后，回顾了药物代谢和分析化学的未来趋势以及它们如何影响代谢稳定性研究。回顾了近期药物化学文献中的一些案例研究，以例证代谢稳定性研究如何影响药物设计并改善生物利用度和半衰期。最后，回顾了药物代谢和分析化学的未来趋势以及它们如何影响代谢稳定性研究。回顾了近期药物化学文献中的一些案例研究，以例证代谢稳定性研究如何影响药物设计并改善生物利用度和半衰期。最后，回顾了药物代谢和分析化学的未来趋势以及它们如何影响代谢稳定性研究。