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山羊去势后经皮应用氟尼辛减轻疼痛的药代动力学及疗效评估。

Evaluation of the pharmacokinetics and efficacy of transdermal flunixin for pain mitigation following castration in goats.

作者信息

Graves Meggan T, Schneider Liesel, Cox Sherry, Caldwell Marc, Krawczel Peter, Lee Amanda, Lear Andrea

机构信息

Large Animal Clinical Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, TN.

Department of Animal Science, University of Tennessee Institute of Agriculture, Knoxville, TN.

出版信息

Transl Anim Sci. 2020 Oct 30;4(4):txaa198. doi: 10.1093/tas/txaa198. eCollection 2020 Oct.

Abstract

The mitigation of pain associated with common management procedures is a rising concern among veterinarians, producers and consumers. Nonsteroidal anti-inflammatory drugs are vital compounds for this purpose due to their cost, convenience, and efficacy. A transdermal formulation of flunixin meglumine (FM) was approved for the treatment of pain in cattle; however, the efficacy has yet to be determined for small ruminants. The current study had two aims: 1) to determine the pharmacokinetics of transdermal flunixin meglumine (TD FM) in bucklings and 2) to evaluate pain mitigation by TD FM following castration. To evaluate pharmacokinetics, 12 male goats (mean age = 6 mo) received 2.2 mg/kg of FM IV ( = 6) or 3.3 mg/kg TD FM ( = 6). Plasma FM concentrations were measured. The mean , , and harmonic mean half-life for TD FM were 1.09 ± 0.65 μg/mL, 5.50 ± 2.95 h, and 7.16 ± 2.06 h, respectively. To evaluate the efficacy of pain mitigation, 18 goats were randomly assigned to three treatment groups: 1) TD FM and castration (FM CAST) ( = 6); 2) transdermal placebo and castration (PL CAST) ( = 6); and 3) TD FM and sham castration (SHAM) ( = 6). Plasma samples were collected at 0, 12, 24, 36, 48, 72, and 96 h to assess cortisol and prostaglandin E (PGE) Daily dry matter intake (DMI) was recorded and body weight was measured at the beginning and end of the study. Thermography (IRT) images of the scrotum, as well as heart rate (HR), respiratory rate (RR), and rectal temperature, were taken twice daily. Separate mixed analysis of variance models were used to test the effects of treatment, time, and their interaction on mean body temperature, IRT, HR, and RR. Autoregressive covariance structure was utilized to account for repeated measures and individual goat DMI prior to the study was added as a covariate. There were no differences in vital parameters, IRT measurements, cortisol, or PGE in animals receiving either TD FM or placebo following castration ( > 0.05). DMI had a treatment by hour interaction and was significantly higher in FM CAST and SHAM groups than the PL CAST group ( = 0.04). Goats in the SHAM group gained weight throughout the study, whereas goats in all other groups lost weight ( = 0.02). Results indicate that TD FM may mitigate pain as demonstrated by increased DMI; however, a single dose may not be sufficient to reduce physiological indicators of pain associated with castration in goats.

摘要

减轻与常见管理程序相关的疼痛是兽医、养殖者和消费者日益关注的问题。非甾体抗炎药因其成本、便利性和有效性,是用于此目的的重要化合物。氟尼辛葡甲胺(FM)的透皮制剂已被批准用于治疗牛的疼痛;然而,其对小反刍动物的疗效尚未确定。本研究有两个目的:1)确定透皮氟尼辛葡甲胺(TD FM)在羔羊中的药代动力学;2)评估TD FM在去势后减轻疼痛的效果。为评估药代动力学,12只雄性山羊(平均年龄 = 6个月)静脉注射2.2 mg/kg的FM(n = 6)或经皮给予3.3 mg/kg的TD FM(n = 6)。测量血浆FM浓度。TD FM的平均Cmax、Tmax和调和平均半衰期分别为1.09±0.65μg/mL、5.50±2.95小时和7.16±2.06小时。为评估减轻疼痛的效果,18只山羊被随机分为三个治疗组:1)TD FM和去势(FM CAST)(n = 6);2)透皮安慰剂和去势(PL CAST)(n = 6);3)TD FM和假去势(SHAM)(n = 6)。在0、12、24、36、48、72和96小时采集血浆样本,以评估皮质醇和前列腺素E(PGE)。记录每日干物质摄入量(DMI),并在研究开始和结束时测量体重。每天两次拍摄阴囊的热成像(IRT)图像,以及心率(HR)、呼吸频率(RR)和直肠温度。使用单独的混合方差分析模型来测试治疗、时间及其交互作用对平均体温、IRT、HR和RR的影响。利用自回归协方差结构来处理重复测量,并且将研究前个体山羊的DMI作为协变量添加。去势后接受TD FM或安慰剂的动物在生命体征参数、IRT测量、皮质醇或PGE方面没有差异(P>0.05)。DMI存在治疗与时间的交互作用,FM CAST和SHAM组的DMI显著高于PL CAST组(P = 0.04)。SHAM组的山羊在整个研究过程中体重增加,而所有其他组的山羊体重减轻(P = 0.02)。结果表明,TD FM可能通过增加DMI来减轻疼痛;然而,单剂量可能不足以降低山羊去势相关疼痛的生理指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f38c/7724925/bc784a657d57/txaa198_fig1.jpg

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