{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T22:47:05Z","timestamp":1775083625258,"version":"3.50.1"},"reference-count":90,"publisher":"American Veterinary Medical Association (AVMA)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"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":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"sc_a1\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To describe the pharmacokinetic parameters of tramadol and its main metabolites, O-desmethyltramadol (M1) and N-desmethyltramadol, and clinically detectable adverse effects after a single orally administered high dose of tramadol in rabbits (\n                      <jats:italic>Oryctolagus cuniculus<\/jats:italic>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a2\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>6 experimental and 1 control healthy intact male rabbits of commercial origin were included in February 2025. Following administration of a 30-mg\/kg oral dose of tramadol, plasma concentrations of tramadol, M1, and N-desmethyltramadol were determined by UHPLC-MS at 12 predetermined time points. Pharmacokinetic parameters were calculated using commercial software. Fecal production and sedation were evaluated before and after the experiment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a3\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean tramadol maximum plasmatic concentration was 91 \u00b1 38 ng\/mL, the average time to reach maximum plasmatic concentration was 40 minutes, the terminal half-life was 4.0 \u00b1 2.4 hours, and the mean area under the curve from the first dose to infinity was 192 \u00b1 45 ng\/hmL. The M1 metabolite reached concentrations compatible with previously described analgesic effects in rabbits after 10 minutes and for up to 3 hours after administration in some individuals, whereas tramadol did not reach analgesic concentrations. Mild sedation was detected in 4 rabbits at the 20 minute- to 6-hour time points, and fecal production increased from 24 to 48 hours after tramadol administration. No clinically relevant adverse effects were noted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a4\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Administration of 30 mg\/kg tramadol, PO, in rabbits results in plasma concentrations of M1 compatible with analgesia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sc_a5\">\n                    <jats:title>Clinical Relevance<\/jats:title>\n                    <jats:p>The short duration of action warrants further studies with long-acting formulations of tramadol.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2460\/ajvr.25.09.0341","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T13:36:27Z","timestamp":1766496987000},"source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of a single high oral dose of tramadol hydrochloride in rabbits (Oryctolagus cuniculus) is compatible with analgesic effect and innocuity"],"prefix":"10.2460","volume":"87","author":[{"given":"Lydie-Amy","family":"Leclerc","sequence":"first","affiliation":[{"name":"D\u00e9partement de Sciences Cliniques, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Beaudry","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biom\u00e9decine V\u00e9t\u00e9rinaire, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Qu\u00e9bec, Canada"},{"name":"Centre Interdisciplinaire de Recherche sur le Cerveau et l\u2019Apprentissage, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Vergneau-Grosset","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Sciences Cliniques, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Saint-Hyacinthe, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1272","reference":[{"issue":"1","key":"B1","series-title":"Vet Clin North Am Exot Anim Pract","first-page":"201","article-title":"Treatment of pain in rabbits","author":"Ozawa S","year":"2023","unstructured":"Ozawa S, Cenani A, Sanchez-Migallon Guzman Lv D. 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