{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:45:15Z","timestamp":1785750315476,"version":"3.56.0"},"reference-count":23,"publisher":"American Veterinary Medical Association (AVMA)","issue":"7","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec id=\"sc_a1\">\n<jats:title>OBJECTIVE<\/jats:title>\n<jats:p>Develop a cytochrome P450 (CYP) phenotyping cocktail for dogs using specific substrates for hepatic P450 enzymes CYP2B11, CYP2D15, and CYP3A12 and determine whether alternative sampling methods (saliva and urine) or single time point samples could be used instead of multiple blood sampling.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a2\">\n<jats:title>ANIMALS<\/jats:title>\n<jats:p>12 healthy client-owned dogs (8 females and 4 males) from February 2019 to May 2019.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a3\">\n<jats:title>METHODS<\/jats:title>\n<jats:p>In a randomized crossover study, dogs received oral administration of the probe drug bupropion (75 mg), dextromethorphan (30 mg), or omeprazole (40 mg) alone or as a 3-drug combination (Program in Individualized Medicine [PrIMe] cocktail) to evaluate simultaneous phenotyping of CYP2B11, CYP2D15, and CYP3A12. Pharmacokinetic profiles for the probe drugs and metabolites were determined using plasma, saliva, and urine. Dogs received probe drugs alone or combined. Pharmacokinetic profiles up to 6 hours postdose for the probe drugs and metabolites were determined using plasma, saliva, and urine.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a4\">\n<jats:title>RESULTS<\/jats:title>\n<jats:p>The PrIMe cocktail was well tolerated. There was no statistically significant interaction between the probe drugs when administered together. Single time point plasma metabolic ratios at 4 hours postdose for all probe drugs strongly correlated with the corresponding area under the plasma concentration-versus-time curve (AUC) ratios. Saliva AUC metabolic ratios for CYP3A12 and CYP2D15 and 6-hour urine for CYP2B11 and CYP2D15 were correlated with plasma AUC ratios.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a5\">\n<jats:title>CONCLUSIONS<\/jats:title>\n<jats:p>The PrIMe cocktail can be used for simultaneous CYP phenotyping using plasma 4-hour single time point sample metabolic ratios. Saliva and urine sampling are suitable for specific CYPs.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sc_a6\">\n<jats:title>CLINICAL RELEVANCE<\/jats:title>\n<jats:p>The PrIMe cocktail has potential as a useful tool in dogs to detect clinically important CYP-mediated drug-drug interactions, identify novel pharmacogenes, determine the drug-metabolizing phenotype of individual dogs, aid in individualized dose selection, and evaluate the effects of various physiological states on drug metabolism.<\/jats:p>\n<\/jats:sec>","DOI":"10.2460\/ajvr.24.02.0049","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:16:31Z","timestamp":1715170591000},"source":"Crossref","is-referenced-by-count":1,"title":["Validation of a bupropion, dextromethorphan, and omeprazole cocktail for simultaneous phenotyping of cytochrome P450 2B11, 2D15, and 3A12 activities in dogs"],"prefix":"10.2460","volume":"85","author":[{"given":"Stephanie E.","family":"Martinez","sequence":"first","affiliation":[{"name":"Program in Individualized Medicine (PrIMe), Comparative Pharmacogenomics Laboratory, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA"},{"name":"Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania E. Perez","family":"Jimenez","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine (PrIMe), Comparative Pharmacogenomics Laboratory, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Court","sequence":"additional","affiliation":[{"name":"Program in Individualized Medicine (PrIMe), Comparative Pharmacogenomics Laboratory, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"issue":"1","key":"B1","series-title":"Pharmacol Ther","first-page":"103","article-title":"Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation","volume":"138","author":"Zanger UM","year":"2013","unstructured":"Zanger UM, Schwab M. 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