Campus Units

Biomedical Sciences, Veterinary Diagnostic and Production Animal Medicine

Document Type


Publication Version

Accepted Manuscript

Publication Date


Journal or Book Title

Current Opinion in Toxicology




The dog is an important species used in preclinical studies in support of human drug product development. Likewise, because of the many active pharmaceutical ingredients (APIs) with therapeutic relevance to both humans and dogs, extrapolation can also occur in the reverse, from human to dog. In either situation, it is important to appreciate species-specific factors influencing drug pharmacokinetics (absorption, metabolism, disposition, and elimination) and the potential impact of disease on the applicability of these extrapolations. Furthermore, tools such as physiologically based pharmacokinetic (PBPK) models not only enable investigators to extrapolate species-specific data on systemic or organ exposure to the parent compound and metabolite(s) but also facilitates an interrogation of factors that can lead to species-specific differences in drug effectiveness and toxicity. In this review, we explore the factors and tools that comprise our current arsenal for understanding and predicting human-canine comparative toxicity.


This is a manuscript of an article published as Martinez, Marilyn N., Jonathan P. Mochel, and Devendra Pade. "Considerations in the Extrapolation Drug Toxicity Between Humans and Dogs." Current Opinion in Toxicology (2020). DOI: 10.1016/j.cotox.2020.05.005.


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