Department of Paraclinical Science, Faculty of Veterinary Science, University of Pretoria, South Africa.
Department of Paraclinical Science, Faculty of Veterinary Science, University of Pretoria, South Africa; Biomedical Research Centre, Faculty of Veterinary Science, University of Pretoria, South Africa.
Comp Biochem Physiol C Toxicol Pharmacol. 2019 Jan;215:41-46. doi: 10.1016/j.cbpc.2018.10.001. Epub 2018 Oct 15.
Asian Gyps vulture species are gradually recovering from the devastating effect of diclofenac being present in contaminated carcasses. This drug was responsible for the death of over 10 million vultures in India, Nepal and Pakistan. To prevent the extinction of vultures, meloxicam was introduced after the ban of veterinary diclofenac. Meloxicam's safety in vultures was attributed to its short elimination half-life in contrast with diclofenac. The reason for the rapid elimination of meloxicam is yet to be explained. The aim of this study was to evaluate the role of biotransformation in the elimination of meloxicam. Six Cape griffon vultures (Gyps coprotheres) were treated with 2 mg/kg meloxicam intramuscularly for faecal and plasma quantification of meloxicam concentration over time. In the plasma meloxicam was characterised by a half-life, mean residence time, clearance and volume of distribution at steady state of 0.37 ± 0.10 h, 0.90 ± 0.12 h, 0.02 ± 0.00 l/h kg and 0.02 ± 0.00 l/kg respectively (presented as geometric mean). Over the 24 h monitoring period, the total non-metabolised meloxicam in the faeces was 1.35 ± 0.71% of the total concentration in the plasma. Based on the short meloxicam elimination half-life and low cumulative concentration of total faecal meloxicam over a period in excess of 10 half-lives, this study indicates that Cape griffon vultures are efficient metaboliser of meloxicam, which is suggestive of different set of cytochrome enzymes being involved in the metabolism to that for diclofenac in this species. Identification of orthologous human CYP2C9 and CYP3A4 enzyme families in vultures will be an important further step in explaining the differences in the metabolic pathway(s) of meloxicam and diclofenac for the species.
亚洲食腐秃鹫物种正在从受污染尸体中存在的双氯芬酸的破坏性影响中逐渐恢复。这种药物导致印度、尼泊尔和巴基斯坦超过 1000 万只秃鹫死亡。为了防止秃鹫灭绝，在禁止使用兽医双氯芬酸后引入了美洛昔康。与双氯芬酸相比，美洛昔康在秃鹫体内短的消除半衰期使其具有安全性。美洛昔康快速消除的原因尚待解释。本研究旨在评估生物转化在美洛昔康消除中的作用。六只南非秃鹫（Gyps coprotheres）接受 2mg/kg 美洛昔康肌内注射，以随时间推移评估粪便和血浆中美洛昔康浓度。在血浆中，美洛昔康的半衰期、平均停留时间、清除率和稳态时的分布容积分别为 0.37±0.10 h、0.90±0.12 h、0.02±0.00 l/h/kg 和 0.02±0.00 l/kg（呈几何平均值）。在 24 小时监测期间，粪便中未代谢的美洛昔康总量为血浆中总浓度的 1.35±0.71%。基于美洛昔康消除半衰期短和超过 10 个半衰期期间粪便中美洛昔康总累积浓度低，本研究表明南非秃鹫是美洛昔康的高效代谢物，这表明该物种中美洛昔康代谢涉及的细胞色素酶与双氯芬酸不同。鉴定秃鹫中同源的人类 CYP2C9 和 CYP3A4 酶家族将是进一步解释美洛昔康和双氯芬酸代谢途径差异的重要步骤。
