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• W3135876263 startingPage "e0247546" @default.
• W3135876263 abstract "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." @default.
• W3135876263 created "2021-03-15" @default.
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• W3135876263 date "2021-03-03" @default.
• W3135876263 modified "2023-10-16" @default.
• W3135876263 title "Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy" @default.
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• W3135876263 doi "https://doi.org/10.1371/journal.pone.0247546" @default.
• W3135876263 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7928481" @default.
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