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

Area of Science:

• Pharmacology
• Drug Development
• Radiochemistry

Background:

• Human absorption, distribution, metabolism, and excretion (hADME) studies are essential for small molecule drug clinical pharmacology.
• These studies utilize ¹⁴C-labeled drugs to determine drug disposition and elimination in humans.

Purpose of the Study:

• To explore evolving strategies and debates surrounding the design and timing of hADME studies.
• To consider the impact of new technologies on reducing radioactive doses in hADME studies.
• To present a framework for future discussions on paradigm shifts in hADME study design.

Main Methods:

• Review of current hADME study strategies across pharmaceutical companies.
• Discussion of the "human first/human only" approach.
• Consideration of technological advancements enabling dose reduction.

Main Results:

• Significant changes in hADME study design have been implemented.
• Newer technologies offer flexibility, particularly in reducing radioactive dosage.
• The "human first/human only" approach has been adopted by some companies.

Conclusions:

• There is an ongoing opportunity to refine hADME study design and timing.
• Technological advancements support more flexible and potentially lower-dose hADME studies.
• Further discussion and a framework are needed to guide future paradigm shifts in hADME studies.