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Recommendations for a Complete Reporting of Statistical Methods in Veterinary Pharmacology 关于兽医药理学统计方法完整报告的建议。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-06 DOI: 10.1111/jvp.70001
Nicolas F. Villarino

Reproducibility and replicability of study results are crucial for advancing scientific knowledge. However, achieving these goals is often challenging, which can compromise the credibility of research and incur immeasurable costs for the progression of science. Despite efforts to standardize reporting with guidelines, the description of statistical methodology in manuscripts often remains insufficient, limiting the possibility of replicating scientific studies. A thorough, transparent, and complete report of statistical methods is essential for understanding study results and mimicking statistical strategies implemented in previous studies. This review outlines the key statistical reporting elements required to replicate statistical methods in most current veterinary pharmacology studies. It also offers a protocol for statistical reporting to aid in manuscript preparation and to assist trialists and editors in the collective strive for advancing veterinary pharmacology research.

研究结果的可重复性和可复制性对于促进科学知识的发展至关重要。然而,实现这些目标往往是具有挑战性的,这可能会损害研究的可信度,并为科学的进步带来不可估量的成本。尽管努力用准则使报告标准化,但手稿中对统计方法的描述往往仍然不足,限制了复制科学研究的可能性。一份全面、透明和完整的统计方法报告对于理解研究结果和模仿以前研究中实施的统计策略至关重要。本综述概述了当前大多数兽药研究中重复统计方法所需的关键统计报告要素。它还提供了统计报告的协议,以帮助手稿准备,并协助试验人员和编辑共同努力推进兽医药理学研究。
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引用次数: 0
Validation and Evaluation of Lateral Flow Tests for the Detection of Antimicrobial Residues on Poultry Feathers 横向流动法检测家禽羽毛中抗菌药物残留的验证与评价。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-03 DOI: 10.1111/jvp.70000
Sophie Hedges, Sophie Mompelat, Dominique Hurtaud-Pessel, Damer P. Blake, Guillaume Fournié, Ludovic Pelligand

Persistence of antimicrobial drugs (AMDs) administered to poultry is longer in feathers than in edible tissues. Hence, poultry feathers are a suitable matrix to investigate historical exposure contributing to antimicrobial resistance, since current detection methods are either non-specific or highly technical and costly. Here we present an analysis of the performance of lateral flow test (LFT) panels in the detection of five AMD classes, namely sulfonamides, tetracyclines, beta-lactams, quinolones, and aminoglycosides, on chicken feather samples. The limit of detection (LOD) of eight AMD substances was determined between 4.7 μg/kg for enrofloxacin and 700 μg/kg for streptomycin. The performance of feather LFT was evaluated for four AMD classes against the reference method (LC–MS/MS). From 79 samples collected from the field, LFT test specificity ranged from 0.63 (quinolones) to 0.95 (tetracyclines). Test sensitivity ranged from 0.15 (beta-lactams) to 0.78 (quinolones and tetracyclines). LFT testing had the greatest discriminatory power for tetracyclines (specificity 0.95 and sensitivity 0.78). LFT had similar test characteristics for sulfonamides and quinolones and performed poorly for beta-lactams. Poor recovery rates (< 15%) were observed in neomycin, kanamycin, and ampicillin. These methods are suitable for preliminarily screening tetracyclines, sulfonamides, and quinolones, with recommendations for further extraction protocols.

给予家禽的抗菌药物(AMDs)在羽毛中的持续时间比在可食用组织中的持续时间长。因此,由于目前的检测方法要么是非特异性的,要么技术含量高、成本高,家禽羽毛是研究导致抗菌素耐药性的历史暴露的合适基质。本文分析了横向流动试验(LFT)面板在鸡毛样品上检测五种AMD的性能,即磺胺类、四环素类、β -内酰胺类、喹诺酮类和氨基糖苷类。8种AMD物质的检出限(LOD)分别为恩诺沙星4.7 μg/kg和链霉素700 μg/kg。对比参考方法(LC-MS/MS),对4种AMD类别的羽毛LFT进行了性能评价。从现场采集的79份样本中,LFT检测特异性从0.63(喹诺酮类药物)到0.95(四环素类药物)不等。试验灵敏度范围从0.15 (β -内酰胺类)到0.78(喹诺酮类和四环素类)。LFT检测对四环素类药物的鉴别能力最强(特异性0.95,敏感性0.78)。LFT对磺胺类药物和喹诺酮类药物具有相似的检测特征,但对β -内酰胺类药物的检测效果较差。回收率低(
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引用次数: 0
Pharmacokinetics of Amoxicillin in the Cat 阿莫西林在猫体内的药代动力学。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-02 DOI: 10.1111/jvp.70003
Ilse R. Dubbelboer, Lena Olsén, Lena Pelander, Marlene Z. Lacroix, Lucie Claustre, Beatrice Roques, Carl Ekstrand

The pharmacokinetics and plasma protein binding of amoxicillin in cats has not been thoroughly investigated. In a single-group sequential designed experimental study, amoxicillin was administered to six healthy cats intravenously, orally, and subcutaneously. Repeated blood samples were drawn after each administration, and amoxicillin concentrations were determined using High Performance Liquid Chromatography coupled to Triple Quadrupole Mass Spectrometry. Plasma amoxicillin data were subjected to population pharmacokinetic analysis, and pharmacokinetic parameters were estimated. The population clearance was 0.18 L/h∙kg, the volume of the central compartment was 0.12 L/kg, the highly perfused compartment was 0.009 L/kg, and the poorly perfused compartment was 0.002 L/kg. The bioavailability was 33% and 69% after oral and subcutaneous administration, respectively. After subcutaneous administration of a slow-release formulation, there was absorption rate-limited pharmacokinetics. The plasma protein binding was 0%–24%. The results increase the understanding of the amoxicillin pharmacokinetics in cats. Further studies combining the results with pharmacodynamic data and in silico simulations are warranted.

阿莫西林在猫体内的药代动力学和血浆蛋白结合尚未被彻底研究。在一项单组顺序设计的实验研究中,研究人员对6只健康猫进行了阿莫西林静脉注射、口服和皮下注射。每次给药后重复抽血,用高效液相色谱-三重四极杆质谱法测定阿莫西林浓度。血浆阿莫西林数据进行人群药代动力学分析,并估计药代动力学参数。种群清除率为0.18 L/h∙kg,中央室容积为0.12 L/kg,高灌注室容积为0.009 L/kg,低灌注室容积为0.002 L/kg。口服和皮下给药后生物利用度分别为33%和69%。皮下给药后缓释制剂,有吸收率有限的药代动力学。血浆蛋白结合率为0% ~ 24%。结果增加了对阿莫西林在猫体内药代动力学的认识。进一步的研究结合药效学数据和计算机模拟的结果是必要的。
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引用次数: 0
Fipronil Tissue Residues and Withdrawal Period Feasibility in Laying Hens After Extra-Label Use 超标签使用后氟虫腈在蛋鸡体内的组织残留及停药期可行性。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-30 DOI: 10.1111/jvp.70002
Lucila Canton, Andrea Berkovic, Laura Ceballos, Candela Canton, Carlos Lanusse, Luis Alvarez, Laura Moreno

Fipronil, a broad-spectrum insecticide, is often used off-label in laying hens to control red mites. This study investigated fipronil residue levels in hen tissues after simulating common extra-label administrations: in-feed (1 mg kg−1 twice) and transdermal (1 mg kg−1 once). Fipronil residues were quantified by HPLC-MS/MS. Both administrations resulted in quantifiable residues in edible tissues (muscle, liver, kidney, skin, fat) and feathers for up to 60 days. Fipronil-sulfone, the primary metabolite, was the dominant residue in tissues. Fat accumulated the highest concentrations. In-feed administration led to higher overall residues in edible tissues, while transdermal application resulted in higher concentrations in feathers. Calculated withdrawal periods, based on established MRLs, ranged from 36 days (muscle, transdermal) to 131 days (fat, transdermal). These long withdrawal periods render both administration routes impractical for poultry production. The study highlights the risk of fipronil residues in poultry products and suggests feather/fecal sampling for monitoring illicit use.

氟虫腈是一种广谱杀虫剂,经常在标签外用于蛋鸡控制红螨。本研究在模拟常见的标签外用药后调查了氟虫腈在母鸡组织中的残留水平:饲料(1 mg kg-1两次)和透皮(1 mg kg-1一次)。采用HPLC-MS/MS法测定氟虫腈残留量。两种药物都导致可食用组织(肌肉、肝脏、肾脏、皮肤、脂肪)和羽毛中可量化残留长达60天。主要代谢物氟虫腈-砜是组织中的主要残留物。脂肪积聚的浓度最高。饲料中施用导致食用组织中总残留较高,而透皮施用导致羽毛中浓度较高。根据确定的MRLs,计算出的停药期从36天(肌肉,透皮)到131天(脂肪,透皮)不等。这些较长的停药期使得这两种给药途径对家禽生产都是不切实际的。该研究强调了氟虫腈残留在家禽产品中的风险,并建议对羽毛/粪便进行取样以监测非法使用。
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引用次数: 0
Pharmacokinetics of Chloramphenicol and Chloramphenicol Glucuronide in Horses Following Administration Per Rectum or via Nasogastric Intubation 氯霉素和氯霉素葡萄糖醛酸盐经直肠或经鼻胃插管给药后在马体内的药代动力学。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-26 DOI: 10.1111/jvp.13520
B. Sayler, A. J. Manship, J. Davis, J. Taylor, L. Gilliam

Chloramphenicol is a broad-spectrum antibiotic used in equine practice. It is known to produce adverse effects of hyporexia/anorexia after oral administration. Administration per rectum (PR) could mitigate the appetite suppression seen with oral administration and allow its use in horses unable to receive oral medications. The objectives of this study were to evaluate the relative bioavailability of chloramphenicol administered PR or via nasogastric tube (NGT) and determine relevant pharmacokinetic/pharmacodynamic parameters and metabolic ratios. Ten healthy, adult horses were administered chloramphenicol tablets (50 mg/kg) PR or via NGT in a randomized crossover design with a washout period. Blood samples were collected at predetermined times over 24 h, and plasma concentrations of chloramphenicol and its inactive metabolite chloramphenicol glucuronide were analyzed using a validated UPLC-MS/MS assay. Chloramphenicol tablets dissolved in water were rapidly metabolized to chloramphenicol glucuronide following both routes. Maximum concentrations for PR and NGT administration were (C max; μg/mL) 0.119 ± 0.135 and 11.7 ± 5.8, respectively. Administration PR resulted in a relative bioavailability of 0.56% ± 0.86%. The metabolic ratio of chloramphenicol glucuronide to chloramphenicol was 20.2 ± 6.19 for PR and 5 ± 1.88 for NGT. Administration of chloramphenicol PR does not reach therapeutic concentrations nor prevent significant metabolism of chloramphenicol. After administration by NGT, plasma concentrations of chloramphenicol exceeded 2 μg/mL for 3.93 ± 0.44 h.

氯霉素是一种广谱抗生素,用于马的实践。已知口服后会产生缺氧/厌食的不良反应。直肠给药(PR)可以减轻口服给药所见的食欲抑制,并允许在无法接受口服药物的马中使用。本研究的目的是评估氯霉素给药和鼻胃管(NGT)的相对生物利用度,并确定相关的药代动力学/药效学参数和代谢比。在随机交叉设计中,10匹健康的成年马被给予氯霉素片(50 mg/kg) PR或NGT。在预定的24小时内采集血样,使用经过验证的UPLC-MS/MS法分析氯霉素及其无活性代谢物氯霉素葡萄糖醛酸盐的血浆浓度。氯霉素片经两种途径均可快速代谢为氯霉素葡萄糖醛酸盐。PR和NGT给药的最大浓度为(Cmax;μg/mL)分别为0.119±0.135和11.7±5.8。给药后的相对生物利用度为0.56%±0.86%。氯霉素葡萄糖醛酸对氯霉素的代谢比PR为20.2±6.19,NGT为5±1.88。氯霉素PR的施用不能达到治疗浓度,也不能阻止氯霉素的显著代谢。NGT给药后,氯霉素血药浓度超过2 μg/mL,持续时间为3.93±0.44 h。
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引用次数: 0
Routine Doses of Enrofloxacin Achieve Pharmacodynamic Target Likely to Treat Susceptible and Susceptible Dose-Dependent Bacterial Infections in Critically Ill Dogs 常规剂量恩诺沙星可达到治疗危重犬易感及易感剂量依赖性细菌感染的药效学目标
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-19 DOI: 10.1111/jvp.13519
Robert Goggs, Sarah Robbins, Julie Menard, Jamie Selman, Jeff Beverly, Sydney Kraus-Mallet, Mark G. Papich

The fluoroquinolones, particularly enrofloxacin, are frequently used to treat life-threatening bacterial infections in small animal emergency and critical care practice. Achieving therapeutic plasma concentrations is essential for effective treatment, whereas inadequate concentrations select for resistance among Enterobacterales and Pseudomonas aeruginosa . We conducted a prospective observational study in 19 critically ill dogs to evaluate the pharmacokinetics (PK) of enrofloxacin and its active metabolite ciprofloxacin after administration of a standardized dosage (10 mg/kg IV q24 h). Plasma concentrations were measured at multiple time points using liquid chromatography-mass spectrometry, and PK modeling was performed to determine best-fit compartmental models. A 2-compartment model best described enrofloxacin PK. There was considerable between-dog variation in PK parameters, likely due to known challenges of drug dosing in critical illness. The percentage conversion of enrofloxacin to ciprofloxacin was lower than has previously been reported in healthy dogs. Pharmacodynamic analyses suggest that enrofloxacin administered at 10 mg/kg IV q24 h to critically ill dogs will likely result in effective treatment of infections by susceptible and susceptible dose-dependent bacteria, and achieved concentrations may be sufficient to reduce the risk of AMR development.

氟喹诺酮类药物,特别是恩诺沙星,在小动物急诊和重症监护实践中经常用于治疗危及生命的细菌感染。达到治疗性血浆浓度对于有效治疗至关重要,而浓度不足则会导致肠杆菌和铜绿假单胞菌产生耐药性。我们对19只危重犬进行了前瞻性观察研究,以评估恩诺沙星及其活性代谢物环丙沙星在给予标准剂量(10 mg/kg IV q24 h)后的药代动力学(PK)。使用液相色谱-质谱法测量多个时间点的血浆浓度,并进行PK建模以确定最适合的室室模型。2室模型最好地描述了恩诺沙星的PK。狗之间的PK参数有相当大的差异,可能是由于已知的危重疾病中药物剂量的挑战。在健康犬中,恩诺沙星转化为环丙沙星的百分比低于先前的报道。药效学分析表明,对危重犬给予10mg /kg IV / 24h的恩诺沙星可能会有效治疗易感细菌和易感剂量依赖细菌的感染,并且达到的浓度可能足以降低AMR发生的风险。
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引用次数: 0
Penicillin and Gentamicin Concentrations in the Uterine Fluid of Non-Pregnant Mares Following a Single Intrauterine Infusion 单次宫内输注后未怀孕母马子宫液中青霉素和庆大霉素的浓度。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-14 DOI: 10.1111/jvp.13518
C. Scott Bailey, Theresa M. Beachler, Jonathan P. Mochel, Larry W. Wulf, Michael Yaeger, Debosmita Kundu, Kate Withowski, Mark G. Papich

Despite their widespread clinical use, there is limited pharmacokinetic data for many equine intrauterine antimicrobials. This study aimed to measure the concentration of gentamicin and penicillin in the uterine fluid of mares following infusion of either a standard (PPGent) or long-acting (LA-PPGent) compounded formulation. We hypothesized that both formulations would result in therapeutic concentrations, with total concentrations sustained for longer using the long-acting formulation. Mares were administered 2400 mg of procaine penicillin and 200 mg of gentamicin via a single intrauterine infusion in either a standard (n = 6) or a lyophilized formulation suspended in a slow-release matrix (n = 6). Intrauterine fluid was collected over a 72-h period and analyzed for antibiotic concentrations using high-performance liquid chromatography and ultra-high-performance liquid chromatography and tandem mass spectrometry. Mean maximal concentrations were seen at 0.5 h in group PPGent (Penicillin: 10,123.0 ± 4298.0 μg/mL, Gentamicin: 3397.3 ± 1338.5 μg/mL) and exceeded MIC for relevant organisms for 72 h (Penicillin: 2.59 ± 6.34 μg/mL, Gentamicin: 2.14 ± 2.4 μg/mL). Interestingly, maximal concentrations were lower in group LA-PPG (Penicillin: 2213.8 ± 967.8 μg/mL—p < 0.05, Gentamicin: 1859 ± 2413 μg/mL) and exceeded MIC for a shorter period of time than the unmodified mixture of commonly used FDA-approved antibiotics.

尽管临床上广泛使用,但许多马宫内抗菌剂的药代动力学数据有限。本研究的目的是测量庆大霉素和青霉素的浓度在母马子宫液后输注标准(PPGent)或长效(LA-PPGent)复方制剂。我们假设两种配方都会产生治疗浓度,使用长效配方总浓度持续时间更长。母马给予24000mg普鲁卡因青霉素和200mg庆大霉素单次宫内输注标准制剂(n = 6)或悬浮在缓释基质中的冻干制剂(n = 6)。采集72h的宫内液,采用高效液相色谱、超高效液相色谱和串联质谱分析抗生素浓度。PPGent组平均最高浓度出现在0.5 h(青霉素:10123.0±4298.0 μg/mL,庆大霉素:3397.3±1338.5 μg/mL),超过相关生物MIC 72 h(青霉素:2.59±6.34 μg/mL,庆大霉素:2.14±2.4 μg/mL)。有趣的是,LA-PPG组最大浓度较低(青霉素:2213.8±967.8 μg/mL-p)
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引用次数: 0
Incorporating the Competencies of Evidence-Based Veterinary Medicine Focused on Pharmacotherapeutics Into Clinical Rotations for Small Animal Dermatology and Food Animal Medicine and Surgery at a Veterinary Medical Teaching Hospital in the US. 在美国兽医教学医院将以药物治疗为重点的循证兽医学的能力纳入小动物皮肤病和食品动物医学和外科的临床轮转。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-12 DOI: 10.1111/jvp.13516
Virginia R Fajt, Adam P Patterson, Dusty Nagy, Jennifer Schleining, Kevin Washburn

Building the skills and knowledge necessary to practice evidence-based veterinary medicine (EBVM) should occur throughout the veterinary curriculum. Operationalizing EBVM includes asking a clinical question in PICO format, searching the biomedical literature for evidence, critically appraising the evidence, and applying the evidence to make a clinical recommendation. At the Texas A&M University College of Veterinary Medicine & Biomedical Sciences, we have embedded EBVM skill-reinforcing assignments into two clinical rotations, Dermatology and Food Animal Medicine and Surgery. In this paper, we describe the implementation and the evolution of assignments, including the learning objectives, workflow, and grading rubrics. We also summarize the types of PICO questions pursued by students. We conclude with the pharmacologist's and the clinicians' reflections on the value of the assignments and the approach of collaboration among specialists.

建立实践循证兽医学(EBVM)所需的技能和知识应该贯穿整个兽医课程。实施EBVM包括以PICO格式提出临床问题,搜索生物医学文献寻找证据,批判性地评估证据,并应用证据提出临床建议。在德克萨斯农工大学兽医与生物医学科学学院,我们将EBVM技能强化任务嵌入到两个临床轮转中,皮肤病学和食品动物医学与外科。在本文中,我们描述了作业的实现和演变,包括学习目标、工作流程和评分标准。我们还总结了学生所追求的PICO问题的类型。我们总结了药理学家和临床医生对任务的价值和专家之间合作的方法的反思。
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引用次数: 0
Dissolution Characteristics of Split and Crushed Levetiracetam Extended-Release Tablets in Comparison With Immediate-Release Formulation 旋碎左乙拉西坦缓释片与速释制剂的溶出特性比较。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-12 DOI: 10.1111/jvp.13517
Alejandra Mondino, Julie A. Nettifee, Mark G. Papich, Karen R. Muñana

Levetiracetam (LEV) is a commonly used antiseizure medication in dogs, available in immediate-release (LEV-IR) and extended-release (LEV-XR) formulations. LEV-XR improves owner compliance with less frequent dosing, but its lowest concentration tablet (500 mg) often exceeds recommended doses for small dogs. This study evaluated how modifying LEV-XR tablets affects dissolution rates, comparing intact, split, and crushed LEV-XR tablets with intact LEV-IR tablets. Dissolution testing followed United States Pharmacopeia (USP) guidelines for LEV-XR tablets. Tablets were placed in a buffer solution (pH 6.0) and agitated at 100 rpm. Samples were collected at 0, 0.5, 2, 4, 6, and 8 h, then analyzed by high-pressure liquid chromatography (HPLC) using a USP reference standard. Results indicated that splitting LEV-XR tablets slightly increased drug release compared to intact tablets, while crushing eliminated extended-release properties, mimicking LEV-IR dissolution. These findings suggest that splitting LEV-XR tablets may be a viable strategy for dosing small dogs without compromising sustained release. Conversely, crushing LEV-XR tablets may be useful for rapid drug release in cluster seizure protocols. Future pharmacokinetic studies are needed to confirm if these in vitro results correlate with in vivo performance for both maintenance and emergency seizure management in dogs.

左乙拉西坦(LEV)是犬类常用的抗癫痫药物,有速释(LEV- ir)和缓释(LEV- xr)两种剂型。LEV-XR通过减少给药频率来改善饲主的依从性,但其最低浓度片剂(500毫克)通常超过小型犬的推荐剂量。本研究评估了修饰LEV-XR片对溶出率的影响,并将完整的、分裂的和粉碎的LEV-XR片与完整的LEV-IR片进行了比较。溶出度测试遵循美国药典(USP) LEV-XR片的指南。将片剂置于pH 6.0的缓冲液中,以100 rpm搅拌。分别于0、0.5、2、4、6、8 h采集样品,使用USP标准品进行高压液相色谱分析。结果表明,与完整片剂相比,拆分后的LEV-XR片剂略微增加了药物释放,而粉碎后的LEV-XR片剂则消除了缓释特性,与LEV-IR溶出相似。这些研究结果表明,拆分LEV-XR片剂可能是一种可行的给药策略,可以在不影响缓释的情况下给小型犬服用。相反,粉碎LEV-XR片可能有助于在集束发作方案中快速释放药物。未来的药代动力学研究需要证实这些体外结果是否与狗的维持和紧急癫痫发作管理的体内表现相关。
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引用次数: 0
A Randomized, Blinded, Placebo-Controlled Crossover Study of the Pharmacokinetics and Pharmacodynamics of Naloxone, Naltrexone, and Nalmefene in Methadone-Sedated Working Dogs 纳洛酮、纳曲酮和纳美芬在美沙酮镇静工作犬体内药代动力学和药效学的随机、盲法、安慰剂对照交叉研究
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-05-08 DOI: 10.1111/jvp.13515
Travis Mills, Mary A. Robinson, Ciara Barr, Darko Stefanovski, Youwen You, Rachel Proctor, Kasey Seizova, Amritha Mallikarjun, Cynthia M. Otto

A randomized, blinded, placebo-controlled crossover study was performed with eight professional working dogs to evaluate the pharmacokinetics and pharmacodynamics of three opioid reversal agents. Following sedation with 1 mg kg−1 methadone HCl IV, dogs were randomly assigned to receive naloxone, naltrexone, or nalmefene at 0.1 mg kg−1 IM, or saline (0.1 mL kg−1). Sedation scores and vital signs were obtained for 6 h, and blood samples were obtained for 72 h. Across all groups and phases, the mean sedation score prior to methadone was 0.93/14, and prior to reversal/placebo was 11.45/14. Mean sedation scores 1 min post reversal/placebo were 7.6, 7.4, 8.1, and 10.6; and at 5 min were 2.2, 1.9, 1.9, and 11.8 for nalmefene, naloxone, naltrexone, and saline, respectively. Dogs with a sedation score ≥ 10/14 at 20 min after reversal/placebo were administered 0.1 mg kg−1 of naloxone IM and included all dogs that received saline. The reversal agents significantly decreased sedation scores within 5 min (p < 0.001) and reversal was maintained for the duration of the study. A previously undetected slower terminal elimination phase was observed for all analytes between 24 and 72 h; however, future studies with additional time points between 6 and 24 h are needed to generate pharmacokinetic estimates for this phase. These reversal agents may be useful for treating sedation in professional working dogs exposed to opioids prior to seeking veterinary care. Pharmacological differences between methadone and higher potency opioids (fentanyl and its derivatives) preclude interpretation of these findings to non-methadone opioids, and further studies are needed.

采用8只专业工作犬进行了随机、盲法、安慰剂对照交叉研究,以评估3种阿片类逆转药物的药代动力学和药效学。在1 mg kg-1盐酸美沙酮镇静后,狗被随机分配给纳洛酮、纳曲酮或纳美芬(0.1 mg kg-1 IM)或生理盐水(0.1 mL kg-1)。观察6 h镇静评分及生命体征,72 h采血。在所有组和阶段,美沙酮前的平均镇静评分为0.93/14,逆转/安慰剂前的平均镇静评分为11.45/14。逆转/安慰剂后1分钟的平均镇静评分分别为7.6、7.4、8.1和10.6;在5分钟时,纳美芬、纳洛酮、纳曲酮和生理盐水分别为2.2、1.9、1.9和11.8。逆转/安慰剂后20分钟镇静评分≥10/14的狗给予0.1 mg kg-1纳洛酮IM,包括所有接受生理盐水的狗。逆转药物在5分钟内显著降低镇静评分(p
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引用次数: 0
期刊
Journal of veterinary pharmacology and therapeutics
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