非洛昔布和美洛昔康对去势和尾断后羔羊肾脏功能和平均日增重的药代动力学及影响。

IF 1.1 4区 农林科学 Q3 VETERINARY SCIENCES
New Zealand veterinary journal Pub Date : 2023-11-01 Epub Date: 2023-07-16 DOI:10.1080/00480169.2023.2232337
K Kongara, G Purchas, Vsr Dukkipati, D Venkatachalam, N Ward, H Hunt, D Speed
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引用次数: 0

摘要

目的:评价和比较IM与口服菲罗昔布和IM美洛昔康的药代动力学,并检测它们对尾部对接和阉割羔羊肾功能和平均日增重(ADG)的影响。方法:75只3-6周龄的雄性罗姆尼羔羊被随机分为5个治疗组(n = 每组15个):IM firocoxib(1 mg/kg);口服firocoxib(1 mg/kg);IM美洛昔康(1 mg/kg);生理盐水(约2 mL,口服);或伪造。治疗给药后,除假手术组外,所有组均进行了热铁尾对接和橡胶环阉割,假手术组未进行上述程序,但动物的处理方式与阉割和尾对接羔羊相同。在1、2、4、6、8、24、48、72、96和120之前采集血样 给药后数小时,并通过液相色谱法和质谱法定量血浆中的药物浓度。在商业实验室测定血浆尿素和肌酸酐浓度。在尾部对接和阉割后2、4和8周记录羔羊体重。药代动力学分析采用非房室法进行。使用混合模型分析比较组间和时间点间的差异。结果:没有证据表明给予IM的菲洛昔布(LSM 18.6(SE 1.4)小时)、口服菲洛昔b(LSM 18.2(SE 1.4h))和给予IM的美洛昔康(LSM 17)之间的血浆消除半衰期存在差异。0(SE 1.4)小时)。Firocoxib(IM)的分布体积(LSM 3.7(SE 0.2)L/kg)明显大于IM美洛昔康(LSM 0.2(SE 0.2(L/kg))。美洛昔康组的羔羊有较高的(p p 结论和临床相关性:两种菲洛昔布制剂的血浆消除半衰期长,分布量大。美洛昔康组ADG出现短暂降低,可能是由于轻度肾毒性。需要对手术后菲洛昔布和美洛昔康对羔羊的剂量反应效应进行比较研究。缩写:ADG:平均每日收益;Cmax:最大浓度;COX:环氧合酶;LOD:检测限;NSAID:非甾体抗炎药;CL:血浆清除率;T1/2el:血浆消除半衰期;Tmax:达到Cmax的时间;Vd:分配量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacokinetics and effect on renal function and average daily gain in lambs after castration and tail docking, of firocoxib and meloxicam.

Aims: To evaluate and compare the pharmacokinetics of IM and oral firocoxib, and IM meloxicam, and detect their effect on renal function and average daily gain (ADG) in lambs undergoing tail docking and castration.

Methods: Seventy-five male Romney lambs, aged 3-6 weeks, were randomised into five treatment groups (n = 15 per group): IM firocoxib (1 mg/kg); oral firocoxib (1 mg/kg); IM meloxicam (1 mg/kg); normal saline (approximately 2 mL, oral); or sham. Following the treatment administration, hot-iron tail docking and rubber ring castration were performed in all groups except the sham group, which did not undergo the procedures, but the animals were handled in the same manner as castrated and tail docked lambs. Blood samples were collected before and 1, 2, 4, 6, 8, 24, 48, 72, 96 and 120 hours after treatment administration, and drug concentrations in plasma were quantified by liquid chromatography and mass spectrometry. Plasma urea and creatinine concentrations were determined at a commercial laboratory. Lamb body weights were recorded before and 2, 4 and 8 weeks after tail docking and castration. The pharmacokinetic analysis was carried out using a non-compartmental approach. Between-group and between-time-point differences were compared using mixed model analyses.

Results: There was no evidence for a difference in plasma elimination half-life between firocoxib given IM (LSM 18.6 (SE 1.4) hours), firocoxib given orally (LSM 18.2 (SE 1.4) hours), and meloxicam given IM (LSM 17. 0 (SE 1.4) hours). Firocoxib (IM) had a significantly greater volume of distribution (LSM 3.7 (SE 0.2) L/kg) than IM meloxicam (LSM 0.2 (SE 0.2) L/kg). Lambs in the meloxicam group had higher (p < 0.05) plasma urea and creatinine concentrations than those in the firocoxib, saline and sham groups. Lambs' ADG was decreased (p < 0.01) compared to the other treatment groups in the 0-2 week period following meloxicam administration.

Conclusions and clinical relevance: Both formulations of firocoxib had a long plasma elimination half-life and large volume of distribution. There was a transient reduction in ADG in the meloxicam group, possibly due to mild renal toxicity. Comparative studies on dose-response effects of firocoxib and meloxicam in lambs following the procedures are required.Abbreviations: ADG: Average daily gain; Cmax: Maximum concentration; COX: Cyclooxygenase; LOD: Limit of detection; NSAID: Non-steroidal anti-inflammatory drugs; CL: Plasma clearance; T1/2el: Plasma elimination half-life; Tmax: Time to achieve Cmax; Vd: Volume of distribution.

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来源期刊
New Zealand veterinary journal
New Zealand veterinary journal 农林科学-兽医学
CiteScore
3.00
自引率
0.00%
发文量
37
审稿时长
12-24 weeks
期刊介绍: The New Zealand Veterinary Journal (NZVJ) is an international journal publishing high quality peer-reviewed articles covering all aspects of veterinary science, including clinical practice, animal welfare and animal health. The NZVJ publishes original research findings, clinical communications (including novel case reports and case series), rapid communications, correspondence and review articles, originating from New Zealand and internationally. Topics should be relevant to, but not limited to, New Zealand veterinary and animal science communities, and include the disciplines of infectious disease, medicine, surgery and the health, management and welfare of production and companion animals, horses and New Zealand wildlife. All submissions are expected to meet the highest ethical and welfare standards, as detailed in the Journal’s instructions for authors.
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