Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee
Drug Metab Dispos. 2023 Jan;51(1):99-104. doi: 10.1124/dmd.121.000739. Epub 2022 Jul 22.
The systematic study of drug metabolism began in the 19th Century, but most of what we know now has been learned in the last 50 years. Drug metabolism continues to play a critical role in pharmaceutical development and clinical practice, as well as contributing to toxicology, chemical carcinogenesis, endocrinology, and drug abuse. The importance of the field will continue, but its nature will continue to develop with changes in analytical chemistry, structural biology, and artificial intelligence. Challenges and opportunities include toxicology, defining roles of genetic variations, and application to clinical issues. Although the focus of this Minireview is cytochrome P450, the same principles apply to other enzymes and transporters involved in drug metabolism. SIGNIFICANCE STATEMENT: Progress in the field of drug metabolism over the past 50 years has helped make the pharmaceutical enterprise what it is today. Drug metabolism will continue to be important. Challenges and opportunities for the future are discussed.
药物代谢的系统研究始于 19 世纪，但我们现在所知道的大部分知识都是在过去 50 年中获得的。药物代谢在药物开发和临床实践中继续发挥着关键作用，同时也为毒理学、化学致癌、内分泌学和药物滥用做出了贡献。该领域的重要性将继续存在，但随着分析化学、结构生物学和人工智能的变化，其性质也将继续发展。挑战和机遇包括毒理学、确定遗传变异的作用，以及应用于临床问题。虽然这篇综述的重点是细胞色素 P450，但同样的原则也适用于参与药物代谢的其他酶和转运体。重要性声明：过去 50 年来药物代谢领域的进展帮助使制药企业成为今天的样子。药物代谢仍将是重要的。讨论了未来的挑战和机遇。
