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美洛昔康制剂在非洲爪蟾,即 Xenopus laevis 中的有效性、安全性和药代动力学。

Effectiveness, Safety, and Pharmacokinetics of Meloxicam Formulations in African-clawed Frogs, Xenopus laevis.

机构信息

1Tri-Institutional Training Program in Laboratory Animal Medicine and Science, The Rockefeller University, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, New York, New York.

2Comparative Bioscience Center, The Rockefeller University, New York, New York.

出版信息

Comp Med. 2024 Oct 31;74(5):336-343. doi: 10.30802/AALAS-CM-24-041. Print 2024 Oct 1.

DOI:10.30802/AALAS-CM-24-041
PMID:39181699
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11524403/
Abstract

Pain management in amphibians is an emerging field of veterinary medicine with only a limited number of analgesics studied for their efficacy. The African-clawed frog, Xenopus laevis, is a popular animal model in research due to its oocyte morphology and embryonic development. We investigated analgesic effects of 2 formulations of meloxicam (standard and extended release [ER]) along with their pharmacokinetics and potential toxicity in this species. Adult female African-clawed frogs (n = 6/group) received either standard (0.2, 0.4, 1, or 5 mg/kg) or ER meloxicam (0.6, 1.2, 3, or 15 mg/kg) injected into the dorsal lymph sac. The acetic acid test (AAT) was performed at -1, 1, 6, 12, 24, 48, and 72 h postadministration to evaluate pain response. In addition, a subset of frogs (n = 2/group) were euthanized 72 h postinjection and submitted for necropsy. There were no significant differences in AAT with both formulations compared with saline control. No signs of meloxicam-induced toxicity with either formulation was present in histology. A pharmacokinetic study was conducted for both the standard and ER formulation of meloxicam at 5 and 15 mg/kg, respectively. Results were consistent with the fact that both formulations of meloxicam were readily absorbed with the standard plasma concentrations peaking at 20.40 µg/mL at 2 h and ER plasma concentration at 30.4 µg/mL at 12 h. The elimination half-life was only determinable for standard formulation (7.74 h). According to the AAT, both formulations of meloxicam did not provide effective analgesia in adult female Xenopus laevis despite reaching high plasma concentrations.

摘要

两栖动物的疼痛管理是兽医领域一个新兴的研究领域,仅有少数几种镇痛药的疗效得到了研究。非洲爪蟾(Xenopus laevis)因其卵母细胞形态和胚胎发育而成为研究中一种受欢迎的动物模型。我们研究了两种美洛昔康制剂(标准制剂和延长释放制剂)在该物种中的镇痛效果、药代动力学和潜在毒性。成年雌性非洲爪蟾(每组 6 只)背部淋巴囊注射标准(0.2、0.4、1 或 5mg/kg)或延长释放美洛昔康(0.6、1.2、3 或 15mg/kg)。在给药后-1、1、6、12、24、48 和 72 小时进行醋酸试验(AAT)以评估疼痛反应。此外,一部分青蛙(每组 2 只)在注射后 72 小时安乐死并进行尸检。与生理盐水对照组相比,两种制剂的 AAT 均无显著差异。两种制剂均未在组织学上出现美洛昔康诱导的毒性迹象。分别在 5 和 15mg/kg 时对标准和 ER 制剂进行了药代动力学研究。结果与事实一致,即两种美洛昔康制剂均易被吸收,标准制剂的血浆浓度在 2 小时时达到峰值(20.40μg/mL),ER 制剂在 12 小时时达到峰值(30.4μg/mL)。仅能确定标准制剂的消除半衰期(7.74 小时)。根据 AAT,尽管两种美洛昔康制剂都达到了较高的血浆浓度,但在成年雌性非洲爪蟾中并没有提供有效的镇痛作用。