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Nine mixed\u2010breed dogs, weighing 15.33\u2009\u00b1\u20092.25\u2009kg, participated in a two\u2010treatment crossover design: G1 received intravenous dipyrone (25\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and G2 received dipyrone (25\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) combined with tramadol (2\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), with a 15\u2010day washout. Blood samples were collected up to 48\u2009h and plasma concentrations analyzed using UPLC\u2013MS\/MS. Pharmacokinetic parameters were calculated using PKSolver 2.0. Normally distributed data were analyzed with the\n                    <jats:italic>t<\/jats:italic>\n                    \u2010test, and non\u2010normal data with the Mann\u2013Whitney test (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05); parameters with significant differences were subjected to Pearson correlation. Analyses were performed using Python. For MAA, Cmax and C0 differed significantly. For AA,\n                    <jats:italic>AUC<\/jats:italic>\n                    <jats:sub>\n                      0\u2013\n                      <jats:italic>t<\/jats:italic>\n                    <\/jats:sub>\n                    ,\n                    <jats:italic>AUC<\/jats:italic>\n                    <jats:sub>0\u2192\u221e<\/jats:sub>\n                    , Cl, and\n                    <jats:italic>MRT<\/jats:italic>\n                    <jats:sub>0\u2192\u221e<\/jats:sub>\n                    differed significantly. Tramadol and its metabolites were also described. The pharmacokinetic interaction between dipyrone and tramadol increased systemic exposure (AUC) of AA and inhibited the conversion of tramadol to M1, without direct changes in the severe adverse effects associated with MAA. Further studies involving nociceptive stimuli and multiple\u2010dose regimens are needed to assess clinical relevance.\n                  <\/jats:p>","DOI":"10.1111\/jvp.70073","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T12:38:59Z","timestamp":1777034339000},"page":"457-470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influence of Tramadol on the Intravenous Pharmacokinetics of Dipyrone Active Metabolites in Dogs"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0319-2696","authenticated-orcid":false,"given":"Andressa Nunes","family":"Mouta","sequence":"first","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn N\u00f3brega","family":"Arcoverde","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robson","family":"dos Anjos Honorato","sequence":"additional","affiliation":[{"name":"Centro Universit\u00e1rio INTA \u2013 UNINTA Rua Ant\u00f4nio Rodrigues Magalh\u00e3es, 359, Dom Expedito Lopes  Sobral Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naft\u00e1li Silva","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio Vinicius Almeida","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gl\u00edcia Cavalcante","family":"Mesquita","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna Deysi Bandeira","family":"Passos","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-1995","authenticated-orcid":false,"given":"Gabriel","family":"Ara\u00fajo\u2010Silva","sequence":"additional","affiliation":[{"name":"Escola de Qu\u00edmica Universidade Do Estado Do Amap\u00e1, Avenida Presidente Vargas, Centro  Macap\u00e1 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-4861","authenticated-orcid":false,"given":"Val\u00e9ria Veras","family":"de Paula","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancia Animal Universidade Federal Rural Do Semi\u2010\u00c1rido (UFERSA)  Mossor\u00f3 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_11_2_1","first-page":"166","volume-title":"Resolu\u00e7\u00e3o Da Diretoria Colegiada\u2010RDC N\u00b0","author":"Ag\u00eancia Nacional de Vigil\u00e2ncia Sanit\u00e1ria","year":"2017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani14060929"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2023.105034"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15108"},{"issue":"4","key":"e_1_2_11_6_1","first-page":"395","article-title":"Tramadol, Pharmacology, Side Effects, and Serotonin Syndrome: A Review","volume":"18","author":"Beakley B. 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