{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:44:53Z","timestamp":1785750293811,"version":"3.56.0"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T00:00:00Z","timestamp":1438214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:p>The dog<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 enzyme is likely an important contributor to the metabolism of veterinary drugs. Dog<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 is expressed in liver, plus it is inducible and polymorphic, creating the potential for intersubject differences in pharmacokinetics. Hence, the ability to probe dog<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 activity and inhibition is relevant toward veterinary drug development and drug\u2013drug interaction assessment. Previous studies have relied on human probes with questionable specificity for<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2, so it was hypothesized that recombinant<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 could be used to find a specific<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 substrate. Intrinsic clearance experiments demonstrated that tizanidine was a substrate of<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2. Profiling of tizanidine metabolites generated by<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 identified the imidazole metabolite that was detectable in dog plasma. The imidazole metabolite was subsequently used to evaluate tizanidine as a<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 probe. Co\u2010administration of the<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A inhibitor enrofloxacin with tizanidine significantly decreased (30%;<jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>3) the formation of the imidazole metabolite vs. control experiments. As enrofloxacin is a weak inhibitor, further studies are required to confirm the sensitivity of tizanidine as an<jats:italic>in\u00a0vivo<\/jats:italic>probe. However, tizanidine may be a more selective<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 probe than phenacetin when conducting<jats:italic>in\u00a0vitro<\/jats:italic>studies due to the presence of other phenacetin\u2010metabolizing enzymes in dog liver microsomes.<\/jats:p>","DOI":"10.1111\/jvp.12256","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T05:09:21Z","timestamp":1438319361000},"page":"122-130","source":"Crossref","is-referenced-by-count":7,"title":["Evaluation of tizanidine as a marker of canine<scp>CYP<\/scp>1A2 activity"],"prefix":"10.1111","volume":"39","author":[{"given":"C. W.","family":"Locuson","sequence":"first","affiliation":[{"name":"Department of Pharmacology Vanderbilt University School of Medicine Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Surgery Vanderbilt University School of Medicine Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Adcock","sequence":"additional","affiliation":[{"name":"Department of Surgery Vanderbilt University School of Medicine Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. S.","family":"Daniels","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Vanderbilt University School of Medicine Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.021196"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2005.00664.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250010021684"},{"key":"e_1_2_6_5_1","first-page":"409","article-title":"Plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin in dogs following single oral administration of enrofloxacin at 7.5, 10, or 20\u00a0mg\/kg","volume":"3","author":"Boothe D.M.","year":"2002","journal-title":"Veterinary Therapeutics"},{"key":"e_1_2_6_6_1","first-page":"1130","article-title":"In vitro comparison of cytochrome P450\u2010mediated metabolic activities in human, dog, cat, and horse","volume":"25","author":"Chauret N.","year":"1997","journal-title":"Drug Metabolism and Disposition"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02467.x"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199651060-00010"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498259609046746"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.106.011064"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.30.11.1206"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2003.12.005"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-012-0707-7"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.1995.tb00603.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498258909043177"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.108.025312"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.036004"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2.6.875"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2013.765445"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.030429"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200411000-00008"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.046136"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.5.1441-1453.2004"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2013.787155"},{"key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/S0022-3565(24)36999-X","article-title":"The prediction of human pharmacokinetic parameters from preclinical and in\u00a0vitro metabolism data","volume":"283","author":"Obach R.S.","year":"1997","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1980.tb01812.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi973011m"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20120636"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2005.00698.x"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2885.2010.01243.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.31.9.1161"},{"key":"e_1_2_6_32_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0022-3565(25)38136-X","article-title":"Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2","volume":"265","author":"Tassaneeyakul W.","year":"1993","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498250412331285436"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.008722"},{"key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/S0026-895X(25)09467-2","article-title":"Isolation of cDNAs coding for three different forms of liver microsomal cytochrome P\u2010450 from polychlorinated biphenyl\u2010treated beagle dogs","volume":"38","author":"Uchida T.","year":"1990","journal-title":"Molecular Pharmacology"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-199753030-00007"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.109.056705"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.111.041848"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.033068"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvp.12256","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvp.12256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.12256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T20:41:40Z","timestamp":1748551300000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.12256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,30]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1111\/jvp.12256"],"URL":"https:\/\/doi.org\/10.1111\/jvp.12256","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,30]]}}}