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1851536 
Journal Article 
Comment 
Radiolabeled mass-balance excretion and metabolism studies in laboratory animals: a commentary on why they are still necessary 
White, RE; Evans, DC; Hop, CE; Moore, DJ; Prakash, C; Surapaneni, S; Tse, FL 
2013 
1 
Xenobiotica
ISSN: 0049-8254
EISSN: 1366-5928 
43 
2 
219-25; discussion 226-7 
English 
22803803 
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. 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. 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.