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

Comparative medicine Pub Date : 2024-10-31 Print Date: 2024-10-01 DOI:10.30802/AALAS-CM-24-041
Glory Leung, Leslie L Diaz, Sebastien Monette, Caroline S Jiang, Ravi Tolwani, Samantha Peneyra
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引用次数: 0

摘要

两栖动物的疼痛治疗是兽医学的一个新兴领域,目前只有有限的几种镇痛药被研究其疗效。非洲爪蛙(Xenopus laevis)因其卵细胞形态和胚胎发育而成为研究中常用的动物模型。我们研究了两种美洛昔康制剂(标准和缓释 [ER])的镇痛效果,以及它们在该物种中的药代动力学和潜在毒性。成年雌性非洲爪蛙(n = 6只/组)背淋巴囊注射标准剂量(0.2、0.4、1或5 mg/kg)或ER剂量(0.6、1.2、3或15 mg/kg)的美洛昔康。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(n = 2/组)在注射后 72 小时安乐死,并进行尸体解剖。与生理盐水对照组相比,两种制剂的AAT均无明显差异。在组织学方面,两种配方均未出现美洛昔康诱导的毒性迹象。对美洛昔康标准制剂和 ER 制剂进行了药代动力学研究,剂量分别为 5 毫克/千克和 15 毫克/千克。结果表明,两种配方的美洛昔康都很容易被吸收,标准血浆浓度在 2 小时后达到峰值 20.40 微克/毫升,ER 血浆浓度在 12 小时后达到峰值 30.4 微克/毫升。AAT显示,尽管美洛昔康的血浆浓度很高,但这两种制剂在成年雌性爪蟾中都不能提供有效的镇痛效果。
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Effectiveness, Safety, and Pharmacokinetics of Meloxicam Formulations in African-clawed Frogs, Xenopus laevis.

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.

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