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Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics

  • Review Article
  • Theme: Celebrating Women in the Pharmaceutical Sciences
  • Published:
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Abstract

This review is a summary of factors affecting the drug pharmacokinetics (PK) of dogs versus humans. Identifying these interspecies differences can facilitate canine-human PK extrapolations while providing mechanistic insights into species-specific drug in vivo behavior. Such a cross-cutting perspective can be particularly useful when developing therapeutics targeting diseases shared between the two species such as cancer, diabetes, cognitive dysfunction, and inflammatory bowel disease. Furthermore, recognizing these differences also supports a reverse PK extrapolations from humans to dogs. To appreciate the canine-human differences that can affect drug absorption, distribution, metabolism, and elimination, this review provides a comparison of the physiology, drug transporter/enzyme location, abundance, activity, and specificity between dogs and humans. Supplemental material provides an in-depth discussion of certain topics, offering additional critical points to consider. Based upon an assessment of available state-of-the-art information, data gaps were identified. The hope is that this manuscript will encourage the research needed to support an understanding of similarities and differences in human versus canine drug PK.

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Acknowledgements

The authors would like to express our appreciation to Drs. Yuching Yang and Xinyuan Zhang, Center for Drug Evaluation and Research, Office of Clinical Pharmacology, FDA, for providing a critique of this manuscript.

Funding

This collaboration is part of the Cooperative Research and Development Agreement (CRADA) between the US FDA Center for Veterinary Medicine and Certara UK Limited, Simcyp Division. No external funding was involved in the development of this manuscript.

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Authors and Affiliations

  1. Office of New Animal Drug Evaluation, Center for Veterinary Medicine, Food and Drug Administration, Rockville, Maryland, 20855, USA

    Marilyn N. Martinez

  2. SMART Pharmacology, Department of Biomedical Sciences, Iowa State University, Ames, Iowa, 50011, USA

    Jonathan P. Mochel

  3. Certara UK Limited, Simcyp Division, 1 Concourse Way, Sheffield, S1 2BJ, UK

    Sibylle Neuhoff & Devendra Pade

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Correspondence to Marilyn N. Martinez.

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As only available study data were used in the development of this manuscript, no additional human or animal testing occurred for the purpose of generating this review.

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JPM is a founder and COO of 3D Health Solutions, Inc. SN and DP are employees and shareholders of Certara UK, Simcyp Division.

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Martinez, M.N., Mochel, J.P., Neuhoff, S. et al. Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics. AAPS J 23, 59 (2021). https://doi.org/10.1208/s12248-021-00590-0

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