Pharmacogenetic and Metabolic Differences Between Dog Breeds: Their Impact on Canine Medicine and the Use of the Dog as a Preclinical Animal Model

Abstract

Abstract. There is limited information describing species related pharmacogenetic differences in animals. Despite the lack of genetic information in veterinary medicine, breed specific responses to endogenous and exogenous substances have been reported across many species. This finding underscores the importance of obtaining insight into the genotypic and phenotypic variation present across breeds. This article provides a summary of the literature pertaining to canine breed differences in physiology, drug response, drug pharmacokinetics, and metabolic idiosyncrasies. The existing knowledge of pedigrees and the known phenotypes and genotypes of dogs provides important information for determining mode of inheritance, penetration, and other major characteristics of heritable traits. Understanding these breed differences will improve canine population predictions (for canine drug products) and may be of value when extrapolating toxicology data from dogs to humans.

Investigation of pharmacokinetic interaction between ivermectin and praziquantel after oral administration in healthy dogs

“…This lower percent body fat can result in higher serum drug concentrations as compared to that seen in breeds with a higher percent body fat (Zoran, Riedesel, & Dyer, ). Breed‐related differences could cause dissimilarities in gastrointestinal transit time, intestinal fermentation, and drug disposition (Fleischer, Sharkey, Mealey, Ostrander, & Martinez, ). It has been reported that the long transition time causes prolongation in both gastric emptying time and small intestine transit time between breeds (Weber et al., ).…”

“…These polymorphisms can lead to differences in drug exposure and could result in breed‐related differences in drug response. Also, the differences in drug response may affect the safety and/or effectiveness of the drug (Fleischer et al., ; Kamimura, ). The T max (5.33 hr) determined in the praziquantel group was longer than the sustained‐release praziquantel tablet (3.2 hr) (Hong et al., ).…”

Le chien dans la pathologie et la génétique comparée: exemples de maladies et de gènes partagés entre l'homme et le chien

“…Sur le plan génétique, pour déterminer les bases molé-culaires de ces affections, les mêmes approches que pour les maladies monogéniques peuvent être réalisées, grâce à davan-tage de cas ; de telles approches ont déjà permis de mettre en évidence des régions chromosomiques candidates pour des maladies auto-immunes comme le lupus érythémateux (Wilbe et al 2010) ou des cancers (Shearin et al 2012). Il est d'ailleurs à noter que pour certains cancers homologues entre les deux espèces, des essais cliniques, de phase 1 et 2 chez le chien, sont déjà en cours aux États-Unis afin d'identifier de nouvelles molécules ou de nouvelles séquences de traitement chez l'homme (Khanna et al 2006;Paoloni & Khanna, 2007 ;Fleischer et al 2008), qui pourront également être utilisées en médecine vétérinaire.…”

Aging Research 2011: Exploring the Pet Dog Paradigm

“…Table 1 summarizes the vast array of phenotypic domains relevant to human healthspan that can be assessed in dogs and that serve as the foundation for the development of a standardized, age-sensitive assessment of canine health. For some variables, such as T cell function, red blood cell mass, and kidney function, age-related decline is well characterized; in other instances, such as breed-specifi c differences in xenobiotic metabolism, the exciting groundwork is being laid (Fleischer et al 2008). Clearly, generating a complete array of age-specifi c data from the more than 350 canine breeds would be a laborious and time-consuming undertaking.…”