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. 2023 Apr;113(4):775-781.
doi: 10.1002/cpt.2691. Epub 2022 Sep 2.

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

Graeme C Young  1 , Douglas K Spracklin  2 , Alexander D James  3 , Mette G Hvenegaard  4 , Graeme Scarfe  5 , David S Wagner  6 , Katrin Georgi  7 , Hanno Schieferstein  7 , Inga Bjornsdottir  8 , Bianca van Groen  9 , Andrea A Romeo  9 , Kenneth C Cassidy  10 , Georges Da-Violante  11 , Bojan Bister  12 , Stefan Blech  12 , Ramaswamy Lyer  13 , Simone I Schulz  14 , Filip Cuyckens  15 , Patricia Moliner  16
Affiliations

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

Graeme C Young et al. Clin Pharmacol Ther. 2023 Apr.

Abstract

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 14 C-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.

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