{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:25:00Z","timestamp":1777080300503,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,17]],"date-time":"2024-03-17T00:00:00Z","timestamp":1710633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"CAPES, Coordination for the Improvement of Higher Education Personnel, Brazil","doi-asserted-by":"publisher","award":["AUX 395\/2018 PGCI"],"award-info":[{"award-number":["AUX 395\/2018 PGCI"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JBS Found for the Amazon Rainforest","award":["AUX 395\/2018 PGCI"],"award-info":[{"award-number":["AUX 395\/2018 PGCI"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Our objective was to assess the pharmacokinetic characteristics of metamizole when administered together with tramadol in a single intravenous dose to donkeys. Ten male animals received 10 mg\u2219kg\u22121 of dipyrone associated with 2 mg\u2219kg\u22121 of tramadol (T2M10) and 25 mg\u2219kg\u22121 of dipyrone with 2 mg\u2219kg\u22121 of tramadol (T2M25). Venous blood samples were taken from groups to determine the pharmacokinetics after drug administration, using initial brief intervals that were followed by extended periods until 48 h. Restlessness and ataxia were observed in two animals in the T2M25 group. Analysis revealed prolonged detectability of tramadol, 4-methylamine antipyrine, 4-aminoantipyrine (up to 24 h), and O-desmethyltramadol (up to 12 h) after administration. Although metamizole and its metabolites showed no significant pharmacokinetic changes, tramadol and O-desmethyltramadol exhibited altered profiles, likely because of competition for the active sites of CYP450 enzymes. Importantly, the co-administration of metamizole increased the bioavailability of tramadol and O-desmethyltramadol in a dose-dependent manner, highlighting their potential interactions and emphasizing the need for further dose optimization in donkey analgesic therapies. In conclusion, metamizole co-administered with tramadol interferes with metabolism and this interference can change the frequency of drug administration and its analgesic efficacy.<\/jats:p>","DOI":"10.3390\/ani14060929","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T08:17:29Z","timestamp":1710749849000},"page":"929","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tramadol and M1 Bioavailability Induced by Metamizole Co-Administration in Donkeys (Equus asinus)"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9073-1995","authenticated-orcid":false,"given":"Gabriel","family":"Ara\u00fajo-Silva","sequence":"first","affiliation":[{"name":"Organic Chemistry and Biochemistry Laboratory, Universidade do Estado do Amap\u00e1, UEAP, Avenida Presidente Vargas, 650, Macap\u00e1 68900-070, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu\u00e3 B.","family":"de Mac\u00eado","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Universidade Federal Rural do Semi-\u00c1rido, 572, Rua Francisco Mota, Presidente Costa e Silva, Mossor\u00f3 59625-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andressa N.","family":"Mouta","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Universidade Federal Rural do Semi-\u00c1rido, 572, Rua Francisco Mota, Presidente Costa e Silva, Mossor\u00f3 59625-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Gl\u00e1ucia C.","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Universidade Federal Rural do Semi-\u00c1rido, 572, Rua Francisco Mota, Presidente Costa e Silva, Mossor\u00f3 59625-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn N.","family":"Arcoverde","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Universidade Federal Rural do Semi-\u00c1rido, 572, Rua Francisco Mota, Presidente Costa e Silva, Mossor\u00f3 59625-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilian G. S.","family":"Solon","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Pharmaceutical Sciences, PPGCF, Universidade Federal do Amap\u00e1, UNIFAP, Rod Juscelino Kubitschek, Km2, Macap\u00e1 68903-419, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 T.","family":"Perez-Urizar","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Universidad Aut\u00f3noma de San Luis Potos\u00ed, 6, Avenida Doutor Manuel Nava, Zona Universitaria, San Luis 78210, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4292-4861","authenticated-orcid":false,"given":"Val\u00e9ria V.","family":"de Paula","sequence":"additional","affiliation":[{"name":"Department of Animal Science, Universidade Federal Rural do Semi-\u00c1rido, 572, Rua Francisco Mota, Presidente Costa e Silva, Mossor\u00f3 59625-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Regan, F.H., Hockenhull, J., Pritchard, J.C., Waterman-Pearson, A.E., and Whay, H.R. 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