The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that V_dss decreased and C_0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 μg/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of ≥1 mg/kg in sheep.

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不同剂量美洛昔康在羊体内的药代动力学

本研究的目的是确定给绵羊静脉注射 0.5、1 和 2 mg/kg 剂量的美洛昔康后药代动力学的变化。这项研究是在六只阿卡拉曼羊身上进行的。美洛昔康按照纵向药代动力学设计，以 0.5、1 和 2 mg/kg 的剂量静脉注射给每只羊，并有 15 天的清除期。使用高效液相色谱-紫外测定美洛昔康的血浆浓度，并通过非房室分析评估药代动力学参数。0.5 mg/kg 剂量下的美洛昔康检测时间长达 48 小时，1 mg/kg 剂量和 2 mg/kg 剂量下的美洛昔康检测时间长达 96 小时。随着剂量从 0.5 mg/kg 增加到 2 mg/kg，最终消除半衰期和浓度与时间曲线下的剂量归一化面积增加，总清除率下降。与1mg/kg剂量相比，确定2mg/kg剂量中V _dss降低且C _{0.083h增加。}据其他物种报告，美洛昔康在 0.5、1 和 2 mg/kg 剂量下的治疗浓度分别为 12、48 和 96 小时 >0.39 μg/mL。这些结果表明，美洛昔康表现出非线性药代动力学，并且当在绵羊中以≥1 mg/kg的剂量静脉注射时快速起效时，将达到不可预测的血浆浓度。