title: Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics.
abstract: The cytochrome P450 (CYP) superfamily constitutes a collection of enzymes responsible for the metabolism of a wide array of endo- and xenobiotic compounds. Much of the knowledge on substrate specificity and genetic identification of the various CYP isoforms is derived from research in rodents and humans and only limited information has been captured in the dog. Currently, there exist many gaps in our knowledge of canine CYP diversity as a result of the paucity of studies focusing on canine CYPs, canine CYP polymorphisms, and the therapeutic consequences of these genetic variants. Challenges engendered by this lack of information is further amplified by inter- and intraspecies differences in the specificity and affinity of substrates and inhibitors, prohibiting a simple extrapolation of probe substances used in human CYP research. This creates a need to develop and validate canine-specific CYP probes. Failure to understand this potential metabolic and pharmacogenomic diversity can also influence the interpretation of data generated in dogs to support human drug development. It is with these objectives in mind that we provide an overview of what is currently known about canine CYPs with the hope that it will encourage further exploration into this important area of research.
authors: Center for Veterinary Medicine, U.S. Food and Drug Administration, 7520 Standish Place, HFV-100, Rockville, MD 20855, USA. marilyn.martinez@fda.hhs.gov
authors: Marilyn N
authors: MN
authors: Martinez
authors: Leposava
authors: L
authors: Antonovic
authors: Michael
authors: M
authors: Court
authors: Mauro
authors: M
authors: Dacasto
authors: Johanna
authors: J
authors: Fink-Gremmels
authors: Butch
authors: B
authors: Kukanich
authors: Chuck
authors: C
authors: Locuson
authors: Katrina
authors: K
authors: Mealey
authors: Michael J
authors: MJ
authors: Myers
authors: Lauren
authors: L
authors: Trepanier
mesh_terms: D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D004285:Dogs / Q000378:metabolism*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010597:Pharmacogenetics / Q000379:methods; D010599:Pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System