Meloxicam is a widely used nonsteroidal anti-inflammatory drug in avian species. However, variability in pharmacokinetic (PK) and pharmacodynamic (PD) parameters in birds warrants species-specific studies for dose and dosing interval optimization. We performed a perioperative PK study of meloxicam (0.5 mg/kg, intravenously) on emus of three different age groups: 3 chicks (5 weeks old, 3.5 kg), 4 juveniles (26 weeks old, 18.8 kg) and 6 adults (66 weeks old, 38.8 kg). A two-compartment population PK model including weight as a significant covariate on clearance and central volume of distribution (V1) best fitted the data. The typical values (20 kg bird) for clearance and V1 were 0.54 L/kg/h and 0.095 L/kg. Both parameters significantly decreased with increasing weight/age. Meloxicam potency and selectivity for COX-1 and COX-2 were measured in whole blood assays (TxB₂ production endpoint). Meloxicam was partially selective in emus (IC₅₀ COX-1:COX-2 = 9.1:1). At the current empirical dose (0.5 mg/kg/24 hr), plasma meloxicam concentration is above IC₅₀ of COX-2 for only 2 hr. PK/PD predicted dose required for 80% COX-2 inhibition over 24 hr were 3.4, 1.4 and 0.95 L/kg/day in chicks, juveniles and adult emus, respectively. The safety, therapeutic efficacy and practicality of modifying the daily dose or dose interval should be considered for dose recommendations in emus.

中文翻译：

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使用非线性混合效应模型研究美洛昔康在不同年龄组鸸鹋（Dromaius novaehollandiae）中的围手术期药代动力学和药效学

美洛昔康是一种广泛用于鸟类的非甾体抗炎药。然而，鸟类的药代动力学 (PK) 和药效学 (PD) 参数的变异性需要针对剂量和给药间隔优化进行物种特异性研究。我们对三个不同年龄组的鸸鹋进行了美洛昔康（0.5 毫克/千克，静脉注射）围手术期 PK 研究：3 只小鸡（5 周大，3.5 千克），4 只幼鸟（26 周大，18.8 千克）和 6 只成年鸸鹋（66周龄，38.8 公斤）。包括重量作为清除率和中心分布容积 (V1) 的重要协变量的两室群体 PK 模型最适合数据。清除率和 V1 的典型值（20 公斤禽类）分别为 0.54 L/kg/h 和 0.095 L/kg。随着体重/年龄的增加，这两个参数都显着下降。₂生产端点）。美洛昔康在鸸鹋中具有部分选择性 (IC ₅₀ COX-1:COX-2 = 9.1:1)。在当前的经验剂量 (0.5 mg/kg/24 小时) 下，血浆美洛昔康浓度仅在 2 小时内高于COX-2 的IC ₅₀。小鸡、幼鱼和成年鸸鹋在 24 小时内抑制 80% COX-2 所需的 PK/PD 预测剂量分别为 3.4、1.4 和 0.95 L/kg/天。对于鸸鹋的剂量推荐，应考虑修改每日剂量或剂量间隔的安全性、治疗效果和实用性。