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美洛昔康缓释制剂皮下注射给伊斯帕尼奥拉亚马逊鹦鹉(Amazona ventralis)后的药代动力学

Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis).

作者信息

Guzman David Sanchez-Migallon, Court Michael H, Zhu Zhaohui, Summa Noémie, Paul-Murphy Joanne R

出版信息

J Avian Med Surg. 2017 Sep;31(3):219-224. doi: 10.1647/2016-202.

DOI:10.1647/2016-202
PMID:28891702
Abstract

Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean C of 23.4 μg/mL (range, 14.7-46.0 μg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

摘要

美洛昔康已被证明在伊斯帕尼奥拉亚马逊鹦鹉(Amazona ventralis)中具有安全且良好的药效学特征,但存在个体差异。在本研究中,我们测定了美洛昔康缓释制剂皮下注射给伊斯帕尼奥拉亚马逊鹦鹉后的药代动力学。本研究使用了12只健康成年鹦鹉,其中6只雄性和6只雌性。在单次注射美洛昔康缓释制剂(3 mg/kg皮下注射)前(时间0)以及注射后0.5、1、2、6、12、24、48、72、96和120小时采集血样。通过高压液相色谱法测定血浆中美洛昔康浓度。通过非房室分析确定药代动力学参数。血浆浓度在1.8小时(范围为0.5 - 6小时)时达到平均Cmax为23.4 μg/mL(范围为14.7 - 46.0 μg/mL),终末半衰期为7.4小时(范围为1.4 - 40.9小时)。个体差异明显,部分鹦鹉(12只中的4只)血浆美洛昔康浓度非常低,这与之前在同一组鸟类中对标准美洛昔康制剂进行的药代动力学研究中报道的高变异性相似。两只鸟在注射部位出现了小的可自行消退的结痂。基于这些结果,美洛昔康缓释制剂可每12至96小时给伊斯帕尼奥拉亚马逊鹦鹉给药以控制疼痛。由于这些结果高度可变,在进行进一步的药代动力学、安全性和药物基因组学评估以确定准确的给药建议并了解高药代动力学变异性之前,不建议在该物种中使用该制剂。

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