{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T09:40:48Z","timestamp":1774690848595,"version":"3.50.1"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T00:00:00Z","timestamp":1614729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Port Macquarie Koala Hospital, NSW"},{"name":"Winifred Violet Scott Charitable Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Tramadol is used as an analgesic in humans and some animal species. When tramadol is administered to most species it undergoes metabolism to its main metabolites M1 or O-desmethyltramadol, and M2 or N-desmethyltramadol, and many other metabolites. This study describes the pharmacokinetic profile of tramadol when a single subcutaneous bolus of 2 mg\/kg was initially administered to two koalas. Based on the results of these two koalas, subsequently 4 mg\/kg as a single subcutaneous injection, was administered to an additional four koalas. M1 is recognised as an active metabolite and has greater analgesic activity than tramadol, while M2 is considered inactive. A liquid chromatography assay to quantify tramadol, M1 and M2 in koala plasma was developed and validated. Liquid chromatography-mass spectrometry confirmed that M1 had been identified. Additionally, the metabolite didesmethyltramadol was identified in chromatograms of two of the male koalas. When 4 mg\/kg tramadol was administered, the median half-life of tramadol and M1 were 2.89 h and 24.69 h, respectively. The M1 plasma concentration remained well above the minimally effective M1 plasma concentration in humans (approximately 36 ng\/mL) over 12 hours. The M1 plasma concentration, when tramadol was administered at 2 mg\/kg, did not exceed 36 ng\/mL at any time-point. When tramadol was administered at 2 mg\/kg and 4 mg\/kg the area under the curve M1: tramadol ratios were 0.33 and 0.50, respectively. Tramadol and M1 binding to plasma protein were determined using thawed, frozen koala plasma and the mean binding was 20% and 75%, respectively. It is concluded that when tramadol is administered at 4 mg\/kg as a subcutaneous injection to the koala, it is predicted to have some analgesic activity.<\/jats:p>","DOI":"10.1371\/journal.pone.0247546","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T19:28:05Z","timestamp":1614799685000},"page":"e0247546","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy"],"prefix":"10.1371","volume":"16","author":[{"given":"Benjamin","family":"Kimble","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Vogelnest","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2622-5721","authenticated-orcid":true,"given":"Peter","family":"Valtchev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-0500","authenticated-orcid":true,"given":"Merran","family":"Govendir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"issue":"5","key":"pone.0247546.ref001","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1111\/jvp.12038","article-title":"Pharmacokinetics of meloxicam in koalas (Phascolarctos 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