Considerations for Human ADME Strategy and Design Paradigm Shift(s) - An Industry White Paper

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 C-14-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.

Automated summary

This paper discusses the importance of human ADME studies and the opportunities to reconsider the study design and timing in light of newer technologies. It provides insights into the current strategies adopted by pharmaceutical companies and ongoing debates around the human first/human only approach. The paper also offers a framework for further shifts in the paradigm.