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

Date
2021-04-27
Authors
Martinez, Marilyn
Mochel, Jonathan
Neuhoff, Sibylle
Pade, Devendra
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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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This article is published as Martinez, Marilyn N., Jonathan P. Mochel, Sibylle Neuhoff, and Devendra Pade. "Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics." The AAPS Journal 23 (2021): 59. DOI: 10.1208/s12248-021-00590-0.

Keywords
ADME, canine-human interspecies extrapolation, metabolism, scaling factors, transporters
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