{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(3)"],"submitter":["Kimble B"],"funding":["Port Macquarie Koala Hospital, NSW","Winifred Violet Scott Charitable Foundation"],"pubmed_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."],"journal":["PloS one"],"pagination":["e0247546"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7928481"],"repository":["biostudies-literature"],"pubmed_title":["Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy."],"pmcid":["PMC7928481"],"pubmed_authors":["Kimble B","Govendir M","Valtchev P","Vogelnest L"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacokinetic profile of injectable tramadol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy.","description":"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.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021","modification":"2024-02-14T23:09:06.354Z","creation":"2021-03-13T08:20:45Z"},"accession":"S-EPMC7928481","cross_references":{"pubmed":["33657107"],"doi":["10.1371/journal.pone.0247546"]}}