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Xenobiotica
the fate of foreign compounds in biological systems
Volume 43, 2013 - Issue 2
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Topics in Xenobiochemistry

Radiolabeled mass-balance excretion and metabolism studies in laboratory animals: a commentary on why they are still necessary

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Pages 219-225 | Received 09 May 2012, Accepted 22 Jun 2012, Published online: 18 Jul 2012
 

Abstract

  1. The necessity of conducting traditional radiolabeled absorption, distribution, metabolism and excretion (ADME) studies in animals during development of new investigative agents has been questioned in a recent review.

  2. We present a compilation of the benefits of such studies in the understanding of the in vivo pharmacological activity and disposition of new drug candidates, including interpretation of preclinical toxicology findings, characterization of circulating metabolites, and determination of principal pathways of clearance. This understanding is valuable in anticipating the human disposition of the drugs and the planning of the clinical development program.

  3. Because of new technologies, evolving regulatory expectations, and increased scientific understanding of the disposition of drugs, the traditional design and timing of both animal and human ADME studies should be reviewed. Innovative “fit-for-purpose” studies may well be a better choice in a particular drug development program than a standard animal ADME “package”. However, we submit that, at this time, radiolabeled animal ADME studies still provide a definitive and irreplaceable component of our understanding of the in vivo actions and behaviors of drugs and should continue to be performed prior to the exposure of large numbers of human subjects to investigative drugs.

Acknowledgments

We gratefully acknowledge valuable discussions of these issues with Drs. Dennis Heller, William G. Humphreys, Gondi Kumar and Jinn Wu.

Declaration of interest

The authors report no conflicts of interest.

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