The human absorption, distribution, metabolism, and excretion (hADME) study is the cornerstone of the clinical pharmacology package for small molecule drugs, providing comprehensive information on the rates and routes of disposition and elimination of drug-related material in humans through the use of ¹⁴C-labeled drug. Significant changes have already been made in the design of the hADME study for many companies, but opportunity exists to continue to re-think both the design and timing of the hADME study in light of the potential offered by newer technologies, that enable flexibility in particular to reducing the magnitude of the radioactive dose used. This paper provides considerations on the variety of current strategies that exist across a number of pharmaceutical companies and on some of the ongoing debates around a potential move to the so called “human first/human only” approach, already adopted by at least one company. The paper also provides a framework for continuing the discussion in the application of further shifts in the paradigm.

中文翻译：

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人类 ADME 策略和设计范式转变的考虑因素 – 行业白皮书


人体吸收、分布、代谢和排泄 (hADME) 研究是小分子药物临床药理学包的基石，通过使用¹⁴ C标记药物。许多公司的 hADME 研究设计已经发生了重大变化，但仍有机会根据新技术所提供的潜力，继续重新思考 hADME 研究的设计和时间安排，特别是能够实现灵活性以减少所使用的放射性剂量的大小。本文提供了对许多制药公司当前存在的各种战略的考虑，以及围绕可能转向所谓的“人类优先/仅人类”方法的一些正在进行的辩论，该方法已经被至少一家公司采用。本文还提供了一个框架，用于继续讨论范式的进一步转变的应用。