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Pharmacokinetics of intraarticular liposomal amphotericin B in goats (Capra aegagrus hircus) 山羊(Capra aegagrus hircus)关节内脂质体两性霉素 B 的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-04-01 DOI: 10.1111/jvp.13442
Joe S. Smith, Grace D. Malla, Jessica D. Garcia, Jessica E. Gebert, Charlene V. Noll, Pierre-Yves Mulon, Heather K. Knych

Lameness is a significant welfare concern in goats. Amphotericin B is used via intraarticular (IA) administration in models to study experimentally induced lameness in large animals. The main objective of this study was to estimate plasma pharmacokinetic (PK) parameters for amphotericin B in goats after a single IA administration. Liposomal amphotericin B was administered to ten Kiko-cross goats at a dose of 10 mg total (range: 0.34–0.51 mg/kg) via IA administration into the right hind lateral distal interphalangeal joint. Plasma samples were collected over 96 h. Amphotericin B concentrations were measured via liquid chromatography/mass spectrometry (LC–MS/MS). A non-compartmental analysis was used to derive PK parameters. Following single IA administration, maximum plasma concentration was estimated at 54.6 ± 16.5 ng/mL, and time to maximum concentration ranged from 6 to 12 h. Elimination half-life was estimated at 30.9 ± 16.5 h, and mean residence time was 45.1 ± 10.4 h. The volume of distribution after IA administration was 13.3 ± 9.4 L/kg. The area under the curve was 1481 ± 761 h*ng/mL. The achieved maximum concentration was less than the observed concentrations for other species and routes of administration. Further research is needed into the pharmacodynamics of IA liposomal amphotericin B in goats to determine specific research strategies.

跛足是山羊的一个重要福利问题。两性霉素 B 可通过关节内给药用于研究大型动物实验性跛行的模型。本研究的主要目的是估算山羊一次IA给药后两性霉素B的血浆药代动力学(PK)参数。通过在右后外侧远端指间关节内注射两性霉素 B 脂质体,给 10 只 Kiko 杂交山羊注射了总剂量为 10 毫克(范围:0.34-0.51 毫克/千克)的两性霉素 B 脂质体。通过液相色谱/质谱法(LC-MS/MS)测量两性霉素 B 的浓度。采用非室分析法得出 PK 参数。单次给药后,最大血浆浓度估计为 54.6 ± 16.5 纳克/毫升,达到最大浓度的时间为 6 至 12 小时。曲线下面积为 1481 ± 761 h*ng/mL。所达到的最大浓度低于其他物种和给药途径的观察浓度。需要进一步研究山羊体内两性霉素 B 脂质体的药效学,以确定具体的研究策略。
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引用次数: 0
Comparative disposition kinetics of oral deracoxib in sheep and goats 绵羊和山羊口服德拉克西布的处置动力学比较。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-28 DOI: 10.1111/jvp.13444
Charbel Fadel, Beata Łebkowska-Wieruszewska, Andrzej Lisowski, Firas Serih, Amnart Poapolathep, Mario Giorgi

This study investigates the pharmacokinetics (PK) of deracoxib (DX), a selective COX-2 inhibitor, in sheep and goats following a single oral dose. DX, approved for dogs, holds potential as an alternative NSAID in small ruminants, particularly in light of heightened concern regarding abomasal ulceration. The study employed an oral administration of DX at a dose of 150 mg/head (sheep and goats), and plasma concentrations were determined after validating a high-performance liquid chromatography method, coupled to a UV detector. The PK parameters, including maximum plasma concentration (C max), time to reach C max (T max), elimination half-life (t 1/2), and area under the curve (AUC), were evaluated through non-compartmental analysis. Results showed detectable DX in plasma up to 48 h, with no observed adverse effects. No significant differences in any PK parameters were noted between sheep and goats. Notably, t 1/2 values were relatively long, at 16.66 h for sheep and 22.86 h for goats. Despite the fact that both species exhibited comparable drug exposure, high individual variability was noted within each species, suggesting to take into account individual variations in response to DX treatment, rather than species-specific considerations. Additional research involving pharmacodynamics and multiple-dose studies is warranted to comprehensively assess the profile of DX in these species.

本研究调查了选择性 COX-2 抑制剂德拉克昔布 (DX) 在绵羊和山羊中单次口服后的药代动力学 (PK)。DX已被批准用于狗,有望成为小反刍动物的替代非甾体抗炎药,特别是考虑到人们对腹腔溃疡的高度关注。该研究采用了口服DX的方法,剂量为150毫克/头(绵羊和山羊),在验证了高效液相色谱法和紫外检测器后测定了血浆浓度。通过非室分析评估了PK参数,包括最大血浆浓度(Cmax)、达到Cmax的时间(Tmax)、消除半衰期(t1/2)和曲线下面积(AUC)。结果显示,血浆中可检测到的 DX 达 48 小时,未观察到不良反应。绵羊和山羊的任何 PK 参数均无明显差异。值得注意的是,t1/2值相对较长,绵羊为16.66小时,山羊为22.86小时。尽管两个物种的药物暴露量相当,但每个物种的个体差异都很大,这表明应考虑到个体对 DX 治疗的反应差异,而不是特定物种的考虑因素。要全面评估 DX 在这些物种中的特性,还需要进行更多涉及药效学和多剂量研究的研究。
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引用次数: 0
Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs 通过 Omnipod® 系统在狗身上皮下注射氯胺酮的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-27 DOI: 10.1111/jvp.13440
Claudia Colón, Peter Early, Karen Muñana, Natasha Olby, Christopher Mariani, Shelby Mancini, Gilad Fefer, Zhong Li, Jessica Briley, Kate Bailey, Duncan Lascelles, Kristen Messenger

Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9–326.1) ng/mL with a Tmax of 60 (30–75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1–71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.

氯胺酮是一种可注射的麻醉剂,具有镇痛和抗抑郁作用,可预防适应性疼痛。氯胺酮会在肝脏中代谢为活性代谢物--诺克司他明。先前的啮齿类动物研究表明,氯胺酮的镇痛效果中多达 30% 是由氯胺酮产生的。氯胺酮通常以静脉注射(IV)或持续输注(CRI)的方式给药,但也可以皮下注射(SC)和肌肉注射(IM)。Omnipod® 是一种无线皮下胰岛素给药装置,可粘附在皮肤上,以皮下持续输注 (CRI) 的方式给药。狗术后使用 Omnipod® 在 1 小时内注射 1 毫克/千克氯胺酮(IB)。药代动力学(PK)显示,氯胺酮的血浆浓度介于 42 至 326.1 纳克/毫升之间。血浆浓度中位峰值为 79.5(41.9-326.1)纳克/毫升,Tmax 为 60(30-75)分钟。在相同的输注药栓后,相应的诺克他敏 PK 显示血浆药物浓度在 22.0 至 64.8 纳克/毫升之间。血浆浓度峰值中位数为 43.0(26.1-71.8)纳克/毫升,Tmax 中位数为 75 分钟。在输注后不到 1 小时的时间里,狗体内氯胺酮血浆浓度的中位峰值超过了 100 纳克/毫升。Omnipod® 系统成功地在犬术后皮下注射了氯胺酮。
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引用次数: 0
Gastrointestinal release site for delayed release and gelatin capsules in healthy dogs 健康狗胃肠道释放缓释胶囊和明胶胶囊的部位。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-22 DOI: 10.1111/jvp.13439
Charles B. Stone, Adam J. Rudinsky, Rebecca J. Urion, Simone B. March, Jenessa A. Winston

Gelatin capsules deliver their contents to the stomach, while delayed-release (DR) capsules are designed to allow delivery to the small intestine. This study evaluated the gastrointestinal release site of DR capsules in six healthy adult dogs compared to gelatin capsules. Both gelatin and DR capsules were filled with barium-impregnated polyethylene spheres (BIPS™), and following enteral administration, release site was assessed using abdominal radiographs at baseline, immediately after ingestion, 15 min post-ingestion, 30 min post-ingestion, and then every 30 min thereafter. The evaluated phases included fasted conditions (phase 1, n = 6), increased meal size (phase 2, n = 2), double encapsulation (phase 3, n = 2), and altered capsule size (phase 4, n = 1). The released site was the stomach in all phases for both capsule types. In phase 1, DR capsules had a significantly prolonged time (median 60 min, range 60–90) to release BIPS™ compared to gelatin capsules (15 min, range 15–30; p = .03). In phase 2 (full meal size), 3 (double encapsulation), and 4 (smaller capsule size) pilot studies, release time was prolonged but still occurred in the stomach. This is similar to the release site for gelatin capsules but differs from the release site for DR capsules in people. This has implications for pharmacologic outcomes for products that are affected by gastric physiology (e.g. fecal microbiota transplantation). Based on this pilot data, clinicians and researchers should not assume DR capsules will allow for intestinal delivery of contents in dogs. Future studies should be conducted on larger and varied populations of dogs.

明胶胶囊可将内容物送入胃部,而缓释(DR)胶囊则可将内容物送入小肠。与明胶胶囊相比,本研究评估了六只健康成年犬体内 DR 胶囊的胃肠道释放部位。明胶胶囊和 DR 胶囊中都填充了钡浸渍聚乙烯球(BIPS™),在肠道给药后,分别在基线、进食后立即、进食后 15 分钟、进食后 30 分钟以及之后每隔 30 分钟使用腹部 X 光片对释放部位进行评估。评估阶段包括空腹状态(第 1 阶段,n = 6)、增加饭量(第 2 阶段,n = 2)、双层封装(第 3 阶段,n = 2)和改变胶囊大小(第 4 阶段,n = 1)。两种胶囊在所有阶段的释放部位都是胃。在第 1 阶段,DR 胶囊释放 BIPS™ 的时间(中位数 60 分钟,范围 60-90)明显长于明胶胶囊(15 分钟,范围 15-30;p = 0.03)。在第 2 阶段(全餐)、第 3 阶段(双重封装)和第 4 阶段(胶囊尺寸较小)的试验研究中,释放时间有所延长,但仍在胃中释放。这与明胶胶囊的释放部位相似,但与 DR 胶囊在人体内的释放部位不同。这对受胃生理影响的产品(如粪便微生物群移植)的药理结果有影响。根据这些试验数据,临床医生和研究人员不应认为 DR 胶囊可以在狗的肠道中输送内容物。未来的研究应该在更大和更多的狗群中进行。
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引用次数: 0
Pharmacokinetic characteristics of florfenicol in green sea turtles (Chelonia mydas) and hawksbill sea turtles (Eretmochelys imbricata) after intramuscular administration 绿海龟(Chelonia mydas)和玳瑁(Eretmochelys imbricata)肌肉注射氟苯尼考的药代动力学特征。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-22 DOI: 10.1111/jvp.13441
Pandaree Sitthiangkool, Amnart Poapolathep, Thanaphan Chomcheun, Oranee Jongkolpath, Kraisiri Khidkhan, Narumol Klangkaew, Napasorn Phaochoosak, Mario Giorgi, Saranya Poapolathep

The pharmacokinetics of florfenicol (FFC) in green sea and hawksbill sea turtles were evaluated following intramuscular (i.m.) administration at two different dosages of 20 or 30 mg/kg body weight (b.w.). This study (longitudinal design) used 5 green sea and 5 hawksbill sea turtles for the two dosages. Blood samples were collected at assigned times up to 168 h. FFC plasma samples were analyzed using validated high-performance liquid chromatography equipped with diode array detection. The pharmacokinetic analysis was performed using a non-compartment approach. The FFC plasma concentrations increased with the dosage. The elimination half-life was similar between the treatment groups (range 19–25 h), as well as the plasma protein binding (range 18.59%–20.65%). According to the surrogate PK/PD parameter (T > MIC, 2 μg/mL), the 20 and 30 mg/kg dosing rates should be effective doses for susceptible bacterial infections in green sea and hawksbill sea turtles.

本研究评估了绿海龟和玳瑁在肌肉注射 20 或 30 毫克/千克体重(b.w.)两种不同剂量的氟苯尼考(FFC)后的药代动力学。这项研究(纵向设计)使用了 5 只绿海龟和 5 只玳瑁海龟,分别服用两种剂量。在指定时间至 168 小时内采集血样。使用配备二极管阵列检测器的高效液相色谱法对 FFC 血浆样本进行分析。药代动力学分析采用非隔室方法进行。FFC 的血浆浓度随着剂量的增加而增加。各治疗组的消除半衰期(19-25 h)和血浆蛋白结合率(18.59%-20.65%)相似。根据代用 PK/PD 参数(T > MIC,2 μg/mL),20 毫克/千克和 30 毫克/千克的剂量应是绿海龟和玳瑁易感细菌感染的有效剂量。
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引用次数: 0
Reply to: Letter to the Editor from Malik et al.: Acute kidney injury following subcutaneous meloxicam administration 回复Malik等人致编辑的信:皮下注射美洛昔康后的急性肾损伤。
IF 1.3 4区 农林科学 Q2 Veterinary Pub Date : 2024-03-10 DOI: 10.1111/jvp.13438
Alex Krekis, Jonathan N. King, Duncan D'Arcy-Howard, Nadene Stapleton, Jonathan Elliott, Ludovic Pelligand
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引用次数: 0
Pharmacokinetic report: Pharmacokinetics of a single oral dose of gabapentin in goats (Capra hircus) 药代动力学报告:山羊(Capra hircus)单次口服加巴喷丁的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-03-01 DOI: 10.1111/jvp.13436
Michael D. Kleinhenz, Darian Davis, Mikaela M. Weeder, Alyssa Leslie, Emily J. Reppert, Kushan Kompalage, Ryan Tucker, Johann F. Coetzee

Gabapentin is used in goats to treat chronic pain associated with lameness. However, pharmacokinetic data and clinical effectiveness trials are lacking. The objective of the study was to describe the pharmacokinetics of gabapentin in goats following a single oral dose. Six Spanish-crossbred goats were enrolled. Each goat was administered gabapentin at a target dose of 15 mg/kg per os. Serial blood samples were collected out to 60 h post-gabapentin administration for plasma gabapentin concentration determination. Plasma samples were analyzed for gabapentin concentration using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Individual animal pharmacokinetic outcomes were determined using non-compartmental analysis. Gabapentin was detectable in the plasma of all goats at 60 h post-administration. The mean (±SD) Cmax was 2.01 ± 0.62 μg/mL which occurred at 8.47 ± 1.9 h. The mean terminal half-life (T1/2) and mean resident time were determined to be 8.52 ± 1.8 and 18.7 ± 4.0 h, respectively. This study indicates gabapentin is absorbed from the gastrointestinal tract of goats. Further research is needed to determine an optimal dose for clinical efficacy in goats.

加巴喷丁用于治疗山羊跛足引起的慢性疼痛。然而,目前尚缺乏药代动力学数据和临床有效性试验。本研究旨在描述山羊单次口服加巴喷丁后的药代动力学。研究共招募了六只西班牙杂交山羊。每只山羊每次口服加巴喷丁的目标剂量为 15 毫克/千克。在服用加巴喷丁后 60 小时内采集连续血样,测定血浆中的加巴喷丁浓度。使用超高压液相色谱法和质谱法分析血浆样本中的加巴喷丁浓度。采用非室分析法确定动物个体的药代动力学结果。给药后 60 小时,所有山羊的血浆中均可检测到加巴喷丁。平均(±SD)Cmax 为 2.01 ± 0.62 μg/mL,出现在 8.47 ± 1.9 h。平均终末半衰期(T1 /2 )和平均驻留时间分别为 8.52 ± 1.8 h 和 18.7 ± 4.0 h。这项研究表明,加巴喷丁可从山羊的胃肠道吸收。要确定对山羊具有临床疗效的最佳剂量,还需要进一步研究。
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引用次数: 0
Letter to the Editor: Acute kidney injury following subcutaneous meloxicam administration 致编辑的信:皮下注射美洛昔康后的急性肾损伤。
IF 1.3 4区 农林科学 Q2 Veterinary Pub Date : 2024-03-01 DOI: 10.1111/jvp.13437
Richard Malik, Matthew K. Wun, Terence King, Rachel Korman
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引用次数: 0
Florfenicol urinary excretion and its potential for treating canine urinary tract infections 氟苯尼考的尿排泄及其治疗犬尿路感染的潜力。
IF 1.3 4区 农林科学 Q2 Veterinary Pub Date : 2024-02-29 DOI: 10.1111/jvp.13434
Kate S. KuKanich, Elayna E. Anderson, Astrid D. Carcamo Tzic, Butch KuKanich

The canine urinary excretion of florfenicol was evaluated to explore its potential for treating urinary tract infections. Nine healthy male intact purpose-bred Beagles and four healthy client-owned dogs each received a single oral dose of florfenicol 20 mg/kg (300 mg/mL parenteral solution) with food. All voluntary urinations were collected for 12 h. Although florfenicol is reportedly bitter tasting, 7/9 Beagles and 4/4 client-owned dogs completely ingested the florfenicol and were enrolled; salivation (n = 1) and headshaking (n = 3) were observed. The last measured urine florfenicol concentrations were variable: Beagles (0.23–3.19 mcg/mL), Pug (3.01 mcg/mL) English Setter (21.29 mcg/mL), Greyhound (32.68 mcg/mL), and Standard Poodle (13.00 mcg/mL). Urine half-life was similar for the Beagles and the Pug, 0.75–1.39 h, whereas the half-life was 1.70–1.82 h for the English Setter, Greyhound, and Standard Poodle. Larger breed dogs exceeded 8 mcg/mL florfenicol (wild-type cutoff) in their urine at 12 h, whereas the Beagles and Pug had <8 mcg/mL; it is unclear if this is an individual, breed, or size difference. These data suggest oral florfenicol may need to be administered q6-12h for canine urinary tract infections, but further data are needed (more enrolled dogs, multiple-dose regimens) before considering clinical trials or breed-specific differences.

为了探索氟苯尼考治疗尿路感染的潜力,我们对氟苯尼考在犬尿液中的排泄量进行了评估。九只健康的雄性纯种比格犬和四只健康的客户饲养的狗分别口服了一次剂量为 20 毫克/千克的氟苯尼考(300 毫克/毫升肠外溶液)和食物。据报道,尽管氟苯尼考的味道很苦,但仍有 7/9 只比格犬和 4/4 只客户饲养的狗完全摄入了氟苯尼考,并进行了登记;观察到了流涎(n = 1)和摇头(n = 3)现象。最后测得的尿液中氟苯尼考浓度各不相同:比格犬(0.23-3.19 微克/毫升)、八哥犬(3.01 微克/毫升)、英国赛特犬(21.29 微克/毫升)、灰猎犬(32.68 微克/毫升)和标准贵宾犬(13.00 微克/毫升)。比格犬和八哥犬的尿液半衰期相似,为 0.75-1.39 小时,而英国猎犬、灰猎犬和标准贵宾犬的半衰期为 1.70-1.82 小时。大型犬在 12 小时后的尿液中氟苯尼考的浓度超过 8 微克/毫升(野生型临界值),而比格犬和八哥犬的尿液中氟苯尼考的浓度仅为 1 微克/毫升(野生型临界值)。
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引用次数: 0
Pharmacokinetic evaluation of oral deracoxib in geese (Anser anser domesticus) 鹅(Anser anser domesticus)口服德拉克西布的药代动力学评估。
IF 1.3 4区 农林科学 Q2 Veterinary Pub Date : 2024-02-29 DOI: 10.1111/jvp.13435
Charbel Fadel, Beata Łebkowska-Wieruszewska, Amnart Poapolathep, Firas Serih, Krzysztof Bourdo, Mario Giorgi

The integration of pain management in veterinary practice, driven by heightened animal welfare concerns, extends to avian species where subtle and nonspecific behavioral signs pose challenges. Given that safety concerns with classical NSAIDs highlight the need for more targeted alternatives in birds, this study explores the pharmacokinetic (PK) properties of Deracoxib (DX), a COX-2 selective NSAID approved for use in dogs, following a single oral administration in geese. Six healthy female geese received 4 mg/kg DX. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma DX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software in a non-compartmental approach. The results indicated a terminal half-life of 6.3 h and a Tmax of 1 h, with no observed adverse effects. While refraining from claiming absolute safety based on a single dose, it is worth highlighting that further safety studies for DX in geese are warranted, suggesting a possibility for intermittent use. In addition, drawing conclusions on efficacy and suitability awaits further research, particularly in understanding COX-2 selectivity and protein binding characteristics specific to geese.

在动物福利问题日益受到关注的推动下,兽医将疼痛治疗纳入了禽类物种的治疗范围,而禽类物种的微妙和非特异性行为体征给治疗带来了挑战。鉴于传统非甾体抗炎药的安全性问题凸显了在鸟类中使用更有针对性的替代品的必要性,本研究探讨了Deracoxib(DX)的药动学(PK)特性,DX是一种COX-2选择性非甾体抗炎药,已被批准用于狗,在鹅体内单次口服给药后的药动学特性。六只健康雌鹅接受了 4 毫克/千克的 DX 给药。分别在 0、0.25、0.5、0.75、1、1.5、2、4、6、8、10 和 24 小时从左翼静脉抽血至肝素化试管。结果表明,DX 的终末半衰期为 6.3 小时,Tmax 为 1 小时,未观察到不良反应。虽然不能根据单次剂量就断言绝对安全,但值得强调的是,有必要对鹅进行进一步的 DX 安全性研究,这表明有可能间歇性使用。此外,关于疗效和适用性的结论还有待进一步研究,尤其是在了解鹅特有的 COX-2 选择性和蛋白质结合特性方面。
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引用次数: 0
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Journal of veterinary pharmacology and therapeutics
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