2242: Understanding the Genetics of Adverse Drug Reactions in Sighthounds
Grant Status: Closed
Abstract
Life-threatening unanticipated reactions to drugs with a narrow margin of safety (such as those used for anesthesia and to treat cancer) are a common concern for dog owners and veterinarians. However, research conducted at Washington State University has enabled development of a simple cheek swab test (the MDR1 gene test) that is now being used by veterinarians to identify dogs that should either avoid or have reduced doses of certain drugs used to treat cancer and parasite infections. Using a similar strategy the investigators have been conducting research to identify the cause of extremely slow recovery from anesthesia (up to several days) in a high proportion of greyhounds, and also in other sighthound breed dogs (such as Scottish deerhound, Borzoi, Whippets, etc.). The investigators have recently discovered a mutation in a gene that is known to be essential for metabolism (breaking down) many commonly used anesthetic drugs (such as propofol), as well as many other drugs used in dogs. Interestingly in addition to sighthound breeds, this gene mutation is also found in some other breeds such as Border Collies. The purpose of this research project is to prove that this mutation can cause decreased drug metabolism, while also determining which drugs and which dog breeds are likely to be most impacted. The ultimate goal of this study is to develop a genetic test that could be used by veterinarians to guide the safe use of these drugs in dogs with the gene mutation.
Publication(s)
Martinez, S. E., Jimenez, T. E. P., & Court, M. H. (2024). Validation of a bupropion, dextromethorphan, and omeprazole cocktail for simultaneous phenotyping of cytochrome P450 2B11, 2D15, and 3A12 activities in dogs. American Journal of Veterinary Research https://doi.org/10.2460/ajvr.24.02.0049
Martinez SE, Pandey AV, Perez Jimenez TE, Zhu Z, Court MH (2024) Pharmacogenomics of poor drug metabolism in greyhounds: Canine P450 oxidoreductase genetic variation, breed heterogeneity, and functional characterization. PLoS ONE 19(2): e0297191. https://doi.org/10.1371/journal.pone.0297191https://doi.org/10.1371/journal.pone.0297191
Martinez, S. E., Shi, J., Zhu, H.-J., Jimenez, T. E. P., Zhu, Z., & Court, M. H. (2019). Absolute quantitation of drug metabolizing cytochrome P450 enzymes and accessory proteins in dog liver microsomes using label-free standard-free analysis reveals inter-breed variability. Drug Metabolism and Disposition, dmd.119.088070. https://doi.org/10.1124/dmd.119.088070
Martinez, S. E., Andresen, M. C., Zhu, Z., Papageorgiou, I., & Court, M. H. (2020). Pharmacogenomics of poor drug metabolism in Greyhounds: Cytochrome P450 (CYP) 2B11 genetic variation, breed distribution, and functional characterization. Scientific Reports, 10(69). doi:10.1038/s41598-019-56660-z
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