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Single intravenous and oral dose pharmacokinetics of the antiseizure medication brivaracetam in healthy cats 在健康猫体内单次静脉注射和口服抗癫痫药物布瓦西坦的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-17 DOI: 10.1111/jvp.13473
Tom Jukier, Chu Zhang, Robert D. Arnold, Amanda Gross

The number of available antiseizure medications with demonstrated efficacy in cats is limited. As such, there is a need to evaluate the pharmacokinetics of newer medications so that proper dosing regimens can be made. Brivaracetam (BRV) is a more potent analogue of levetiracetam, and is Food and Drug Administration approved for use in people. The goal of this study was to describe the pharmacokinetics of intravenous and oral doses of BRV in healthy cats. A cross-over study involving eight healthy cats, that were administered 10 mg of BRV intravenously as a bolus and orally in the fasted state. Blood samples were collected over 24 h. Analysis was performed using liquid chromatography-mass spectrometry. Data were subjected to non-compartmental analysis. Median (min–max) of maximal concentration, time to maximal concentration, area under the curve, elimination half-life and oral absolute bioavailability were 902 (682–1036) ng/mL, 0.6 (0.5–2.0) h, 6.4 (5.2–7.2) h, 8145 (6669–9351) ng × h/mL and 100% (85–110) respectively. BRV appeared to be well tolerated by all cats. A single dose of BRV is well tolerated both orally and intravenously. Maximal concentrations are produced rapidly and within the human reference interval considered to be therapeutic.

经证实对猫有疗效的抗癫痫药物数量有限。因此,有必要对较新药物的药代动力学进行评估,以便制定适当的用药方案。布里瓦西坦(Brivaracetam,BRV)是左乙拉西坦的一种药效更强的类似物,已被美国食品药品管理局批准用于人类。本研究的目的是描述健康猫静脉注射和口服 BRV 的药代动力学。这项交叉研究涉及 8 只健康猫,分别在空腹状态下静脉注射和口服 10 毫克 BRV。采用液相色谱-质谱法进行分析。对数据进行了非室分析。最大浓度中值(最小-最大)、达到最大浓度的时间、曲线下面积、消除半衰期和口服绝对生物利用度分别为 902(682-1036)纳克/毫升、0.6(0.5-2.0)小时、6.4(5.2-7.2)小时、8145(6669-9351)纳克×小时/毫升和 100%(85-110)。所有猫都能很好地耐受 BRV。口服和静脉注射单剂量 BRV 的耐受性都很好。最大浓度的产生速度很快,且在被认为具有治疗作用的人类参考区间内。
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引用次数: 0
Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (Zalophus californianus) and Pacific harbor seal (Phoca vitulina richardii) 加州海狮(Zalophus californianus)和太平洋海豹(Phoca vitulina richardii)单次口服美洛昔康的药代动力学比较。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-14 DOI: 10.1111/jvp.13469
Emily J. Trumbull, Mark G. Papich, Mattison Peters, Emily R. Whitmer, Michelle Rivard, Cara L. Field

Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (Zalophus californianus: CSL; n = 13) and Pacific harbor seals (Phoca vitulina richardii: PHS; n = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (Cmax) was 0.33 μg/mL with an elimination half-life (Ke t½) of 31.53 h. In CSL, Cmax was 0.17 μg/mL with Ke t½ of 32.71 h. All animals enrolled completed the study without outward adverse clinical signs. The elimination half-life was longer than previously recommended dosing intervals for pinnipeds; however, we cannot speculate in the optimum clinical dose from these results.

药代动力学研究调查了美洛昔康(一种非甾体类消炎药)在多种非家养动物中的剂量策略;但是,此前还没有研究调查过针对针鱼的有充分依据的剂量。要制定给药方案,就需要药代动力学信息,并研究不同种类的松狮之间的差异。显然,健康的加州海狮(Zalophus californianus: CSL; n = 13)和太平洋港海豹(Phoca vitulina richardii: PHS; n = 17)已完成康复,它们被纳入了一项基于群体的药代动力学研究。每只动物口服一次 0.1 毫克/千克的美洛昔康,在 96 小时的研究期间,每只动物在不同时间间隔采集两次血液样本。通过高压液相色谱法测定血浆中的美洛昔康浓度。数据采用非线性混合效应模型(Phoenix® NLME™, Certara, St.)结果表明,在 PHS 中,血浆峰浓度(Cmax)为 0.33 μg/mL,消除半衰期(Ke t½ )为 31.53 h;在 CSL 中,Cmax 为 0.17 μg/mL,Ke t½ 为 32.71 h。消除半衰期长于之前推荐的针鼹鼠用药时间间隔;但是,我们无法根据这些结果推测最佳临床剂量。
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引用次数: 0
Sodium glucose transporter 2 inhibitors: Will these drugs benefit non-diabetic veterinary patients with cardiac and kidney diseases? 钠葡萄糖转运体 2 抑制剂:这些药物对患有心脏和肾脏疾病的非糖尿病兽医患者有益吗?
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-13 DOI: 10.1111/jvp.13472
Jonathan Elliott, Mark A Oyama

Sodium glucose transporter type 2 (SGLT2) inhibitors have been introduced into human medicine where their beneficial effects go beyond the expected improvement in blood glucose control. These drugs appear to prevent progression of both cardiovascular and kidney diseases, not only in diabetic but also in non-diabetic human patients. As these drugs have received conditional approval for use in diabetic cats and are being used in other veterinary species, the intriguing question as to whether they will have similar cardioprotective and nephroprotective effects in dogs and cats is being asked. The primary mechanism(s) by which SGLT2 inhibitors are cardio- and nephroprotective remain to be fully characterized. This paper reviews these suggested mechanisms in the context of the pathophysiology of progressive cardiovascular and kidney diseases in dogs and cats with the goal of predicting which categories of non-diabetic veterinary patients these drugs might be of most benefit.

钠葡萄糖转运体 2 型(SGLT2)抑制剂已被引入人类医疗领域,其有益效果超出了预期的血糖控制改善。这些药物似乎不仅能防止糖尿病患者的心血管疾病和肾脏疾病恶化,还能防止非糖尿病人类患者的心血管疾病和肾脏疾病恶化。由于这些药物已获得用于糖尿病猫的有条件批准,并正被用于其他兽医物种,人们提出了一个耐人寻味的问题:这些药物是否会对猫狗产生类似的心血管和肾脏保护作用?SGLT2 抑制剂具有心血管和肾脏保护作用的主要机制仍未完全确定。本文从猫狗进行性心血管疾病和肾脏疾病的病理生理学角度回顾了这些机制,旨在预测这些药物对哪类非糖尿病兽医患者最有益。
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引用次数: 0
Sodium-glucose transport protein 2 inhibitor use in the management of insulin dysregulation in ponies and horses. 钠-葡萄糖转运蛋白 2 抑制剂用于治疗小马和马的胰岛素失调。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-10 DOI: 10.1111/jvp.13470
Nicola J Menzies-Gow, Edward J Knowles

Laminitis is a common and painful condition of the equine foot and approximately 90% of cases are associated with insulin dysregulation (ID) that is a central feature of the common endocrine disorder equine metabolic syndrome (EMS) and occurs in a subset of animals with pituitary pars intermedia dysfunction. Additional features of EMS include obesity, altered circulating concentrations of adipokines (particularly adiponectin and leptin) and hypertriglyceridaemia. Obesity, ID, hypoadiponectinaemia, hyperleptinaemia and an altered plasma lipid profile are also features of human metabolic syndrome (HMS) alongside hyperglycaemia. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of oral hypoglycaemic agents used in combination with lifestyle changes in the management of HMS. SGLT2 receptors are responsible for 90% of the renal glucose reabsorption that occurs in the proximal convoluted tubule. Thus, these drugs increase urinary glucose excretion by suppressing glucose reabsorption from the glomerular filtrate resulting in urinary calorie loss with consequent weight loss and improvements in ID, hyperglycemia, hypoadiponectinaemia and hyperleptinaemia. There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses. Thus, the use of SGLT2i for the control of equine hyperinsulinaemia with the goal of improving recovery from associated active laminitis or preventing future laminitis has recently been advocated. There are a small number of published studies reporting the use of the SGLT2i canagliflozin, ertugliflozin and velagliflozin to aid the management of equine ID. However, the doses used are largely extrapolated from human studies with limited consideration of species-specific variations. In addition, there is limited evaluation of the fundamental differences between ID in horses and humans, particularly the fact that most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs. Further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses.

蹄叶炎是马蹄部常见的一种疼痛症状,约 90% 的病例与胰岛素失调 (ID) 有关,而胰岛素失调是常见的内分泌失调性疾病马代谢综合征 (EMS) 的一个核心特征,发生在垂体中叶旁功能障碍的动物中。EMS 的其他特征还包括肥胖、脂肪因子(尤其是脂肪连素和瘦素)循环浓度改变和高甘油三酯血症。肥胖、ID、低脂联素血症、高瘦素血症和血浆脂质谱改变也是人类代谢综合征(HMS)的特征,此外还有高血糖。钠-葡萄糖共转运体 2 抑制剂(SGLT2i)是一类新型口服降糖药,在治疗 HMS 的过程中与改变生活方式相结合使用。SGLT2 受体负责近端曲小管中 90% 的肾葡萄糖重吸收。因此,这些药物通过抑制肾小球滤液对葡萄糖的重吸收来增加尿糖排泄,从而减少尿中热量,进而减轻体重,改善 ID、高血糖、低脂血和高瘦血症。目前还没有获得许可的兽药可用于治疗 ID 和预防马匹胰岛素相关性蹄叶炎。因此,最近有人主张使用 SGLT2i 来控制马的高胰岛素血症,以改善相关活动性蹄叶炎的恢复或预防未来的蹄叶炎。有少量已发表的研究报告称,SGLT2i Canagliflozin、ertugliflozin 和 velagliflozin 可用于辅助治疗马匹 ID。然而,所使用的剂量大多是从人类研究中推断出来的,对物种的特异性差异考虑有限。此外,对马匹和人类 ID 基本差异的评估也很有限,特别是大多数患有 ID 的马匹仍然存在高胰岛素血症,但血糖正常,因此尿液中葡萄糖流失的增加可能无法解释这些药物的有益作用。需要进一步研究治疗相关高甘油三酯血症的潜在有害影响,以及 SGLT2i 疗法对马体内脂肪因子循环浓度的影响。
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引用次数: 0
Doxycycline pharmacokinetics and tissue depletion in striped catfish (Pagasianodon hypophthalmus) after oral administration. 口服多西环素后带鱼的药代动力学和组织损耗。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-10 DOI: 10.1111/jvp.13471
Pham Quang Vinh, Nguyen Quoc Thinh, Mathias Devreese, Siska Croubels, Dang Thi Hoang Oanh, Anders Dalsgaard, Masashi Maita, Tran Minh Phu

The pharmacokinetics and residue depletion of doxycycline (DOX) in striped catfish (Pagasianodon hypophthalmus) after oral dosage were investigated. The pharmacokinetic experiment was conducted in an aquarium, while the experiment of residue depletion was performed in both an aquarium and earth ponds. Medicated feed was administered orally using the gavage method at a dosage of 20 mg/kg body weight. Blood, liver, and kidney from medicated fish samples were collected. In the depletion experiments, fish were fed medicated feed for five consecutive days at a dosage of 20 mg/kg body weight, with samples collected during and after medication. The concentrations of DOX were quantified using an LC-MS/MS system. The pharmacokinetics parameters of DOX in striped catfish included the absorption rate constant (ka), absorption half-life (T1/2abs), maximal plasma concentration (Cmax), time to maximal plasma concentration (Tmax), and area under the plasma concentration-time curve from time 0 to 96 h (AUC0-96 h) which were 0.12 h-1, 5.68 h, 1123.45 ng/mL, 8.19 h, and 25,018 ng/mL/h, respectively. Residue depletion results indicated that the withdrawal times of DOX in muscle (with skin) from fish kept in the aquarium were slightly longer than that in fish raised in earth ponds, corresponding to 194 degree-days compared with 150 degree-days. In conclusion, administration of DOX at the dosage of 20 mg/kg body weight can be used for treatment of bacterial infections in striped catfish, and a withdrawal time of 5 days at 29.4°C will ensure consumer food safety due to the rapid depletion of DOX from muscle and skin.

研究了多西环素(DOX)在带鱼(Pagasianodon hypophthalmus)口服后的药代动力学和残留消耗。药代动力学实验在水族箱中进行,而残留物消耗实验则在水族箱和土池中进行。采用灌胃法口服给药饲料,剂量为 20 毫克/千克体重。收集用药鱼的血液、肝脏和肾脏样本。在耗竭实验中,以每公斤体重 20 毫克的剂量给鱼连续喂食五天药物饲料,并在用药期间和用药后采集样本。使用 LC-MS/MS 系统对 DOX 的浓度进行定量。DOX在带鱼体内的药代动力学参数包括吸收率常数(ka)、吸收半衰期(T1/2abs)、最大血浆浓度(Cmax)、达到最大血浆浓度的时间(Tmax)和从0到96小时的血浆浓度-时间曲线下面积(AUC0-96 h),分别为0.12 h-1、5.68 h、1123.45 ng/mL、8.19 h和25 018 ng/mL/h。残留消耗结果表明,水族箱养鱼肌肉(连皮)中 DOX 的撤出时间略长于土塘养鱼,分别为 194 度日和 150 度日。总之,以每公斤体重 20 毫克的剂量服用 DOX 可用于治疗带鱼的细菌感染,由于肌肉和皮肤中 DOX 的快速消耗,29.4°C 下 5 天的停药时间可确保消费者的食品安全。
{"title":"Doxycycline pharmacokinetics and tissue depletion in striped catfish (Pagasianodon hypophthalmus) after oral administration.","authors":"Pham Quang Vinh, Nguyen Quoc Thinh, Mathias Devreese, Siska Croubels, Dang Thi Hoang Oanh, Anders Dalsgaard, Masashi Maita, Tran Minh Phu","doi":"10.1111/jvp.13471","DOIUrl":"https://doi.org/10.1111/jvp.13471","url":null,"abstract":"<p><p>The pharmacokinetics and residue depletion of doxycycline (DOX) in striped catfish (Pagasianodon hypophthalmus) after oral dosage were investigated. The pharmacokinetic experiment was conducted in an aquarium, while the experiment of residue depletion was performed in both an aquarium and earth ponds. Medicated feed was administered orally using the gavage method at a dosage of 20 mg/kg body weight. Blood, liver, and kidney from medicated fish samples were collected. In the depletion experiments, fish were fed medicated feed for five consecutive days at a dosage of 20 mg/kg body weight, with samples collected during and after medication. The concentrations of DOX were quantified using an LC-MS/MS system. The pharmacokinetics parameters of DOX in striped catfish included the absorption rate constant (k<sub>a</sub>), absorption half-life (T<sub>1/2abs</sub>), maximal plasma concentration (C<sub>max</sub>), time to maximal plasma concentration (T<sub>max</sub>), and area under the plasma concentration-time curve from time 0 to 96 h (AUC<sub>0-96 h</sub>) which were 0.12 h<sup>-1</sup>, 5.68 h, 1123.45 ng/mL, 8.19 h, and 25,018 ng/mL/h, respectively. Residue depletion results indicated that the withdrawal times of DOX in muscle (with skin) from fish kept in the aquarium were slightly longer than that in fish raised in earth ponds, corresponding to 194 degree-days compared with 150 degree-days. In conclusion, administration of DOX at the dosage of 20 mg/kg body weight can be used for treatment of bacterial infections in striped catfish, and a withdrawal time of 5 days at 29.4°C will ensure consumer food safety due to the rapid depletion of DOX from muscle and skin.</p>","PeriodicalId":17596,"journal":{"name":"Journal of veterinary pharmacology and therapeutics","volume":" ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SGLT2 inhibitor use in the management of feline diabetes mellitus. 在猫科动物糖尿病治疗中使用 SGLT2 抑制剂。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-02 DOI: 10.1111/jvp.13466
Audrey K Cook, Ellen Behrend

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are routinely used in the management of human type 2 diabetes and have been shown to effectively mitigate hyperglycemia and reduce the risks of cardiovascular and renal compromise. Two SGLT2 inhibitors, namely bexagliflozin and velagliflozin, were recently FDA approved for the treatment of uncomplicated feline diabetes mellitus. These oral hypoglycemic agents are a suitable option for many newly diagnosed cats, with rapid improvements in glycemic control and clinical signs. Suitable candidates must have some residual β-cell function, as some endogenous insulin production is required to prevent ketosis. Appropriate patient selection and monitoring are necessary, and practitioners should be aware of serious complications such as euglycemic diabetic ketoacidosis.

钠-葡萄糖共转运体-2(SGLT2)抑制剂是治疗人类 2 型糖尿病的常规药物,已被证明能有效缓解高血糖症状,降低心血管和肾脏受损的风险。最近,美国食品及药物管理局批准了两种 SGLT2 抑制剂(即 bexagliflozin 和 velagliflozin)用于治疗无并发症的猫科动物糖尿病。这些口服降糖药是许多新确诊猫咪的合适选择,可迅速改善血糖控制和临床症状。合适的患者必须有一些残余的β细胞功能,因为需要一些内源性胰岛素分泌来防止酮症。有必要对患者进行适当的选择和监测,从业人员应注意优生糖尿病酮症酸中毒等严重并发症。
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引用次数: 0
The phenomenon of predatory journals and awareness among researchers in veterinary medicine: Correspondence 掠夺性期刊现象与兽医学研究人员的认识:通信。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-27 DOI: 10.1111/jvp.13468
Hineptch Daungsupawong, Viroj Wiwanitkit
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引用次数: 0
Pharmacokinetics of nalbuphine administered intravenously and subcutaneously in goats (Capra aegagrus hircus) 山羊(Capra aegagrus hircus)静脉注射和皮下注射纳布啡的药代动力学。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-27 DOI: 10.1111/jvp.13463
Jessica D. Garcia, Joe S. Smith, David Minich, Makenna Hopson, Rebecca Rahn, Chiara Hampton, Meggan Graves, Geneviève Bussières, Pierre-Yves Mulon, Lisa S. Ebner, Sherry Cox

The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10-day washout period between sample collection phases. Eighteen plasma samples were collected over a 36-hour period, analyzed using reverse phase high-performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), concentration at time zero (C0), and total body clearance were 120.4 ± 39.1 (min−1 ± SD), 17311.01 ± 7227.32 (min·ng·mL−1 ± SD), 675.6 ± 337.13 (ng·mL−1 ± SD), and 44.5 ± 13.8 (mL·min−1·kg−1 ± SD), respectively. After SC nalbuphine administration, elimination half-life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), and maximum plasma drug concentration were 129 ± 52.9 (min−1 ± SD), 20826.5 ± 14376.2 (min·ng·mL−1), and 368.03 ± 503.78 (ng·mL−1). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future.

本研究旨在评估家山羊静脉注射(IV)和皮下注射(SC)纳布啡的药代动力学(PK)。通过静脉注射和皮下注射两种途径给六只山羊注射盐酸纳布啡,剂量均为 0.8 毫克/千克,样本采集阶段之间至少有 10 天的冲洗期。在 36 小时内收集了 18 份血浆样本,并使用反相高效液相色谱法(HPLC)进行分析。血浆数据采用区室和非区室方法进行分析。静脉注射纳布啡后,消除半衰期、从时间 0 到无穷大的血浆浓度时间曲线下面积(AUC0 - ∞)、零时浓度(C0)和体内总清除率分别为 120.4 ± 39.1(min-1 ± SD)、17311.01 ± 7227.32(min-ng-mL-1 ± SD)、675.6 ± 337.13(ng-mL-1 ± SD)和 44.5 ± 13.8(mL-min-1-kg-1 ± SD)。纳布啡经皮下注射后,消除半衰期、血浆浓度时间曲线下从 0 到无穷大的面积(AUC0 - ∞)和最大血浆药物浓度分别为 129 ± 52.9(min-1 ± SD)、20826.5 ± 14376.2(min-ng-mL-1)和 368.03 ± 503.78(ng-mL-1)。经皮下注射途径计算的生物利用度为 138 ± 126(% ± SD)。纳布啡在山羊体内的特点是消除快、皮下生物利用度高,未来可能成为山羊的一种安全镇痛阿片类药物。
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引用次数: 0
Oclacitinib (APOQUEL®) is a selective Janus kinase 1 inhibitor with efficacy in a canine model of flea allergic dermatitis 奥克替尼(APOQUEL®)是一种选择性 Janus 激酶 1 抑制剂,在犬跳蚤过敏性皮炎模型中具有疗效。
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-26 DOI: 10.1111/jvp.13462
Andrea J. Gonzales, Michelle Aleo, Sean Mahabir, James Messamore, Michael Stegemann

Oclacitinib is a novel Janus kinase (JAK) inhibitor that potently inhibits JAK1-dependent cytokines involved in allergy, inflammation, and pruritus (IL-2, IL-4, IL-6, IL-13, and IL-31). Oclacitinib (Apoquel®, Zoetis Inc, Parsippany, NJ) is approved for the treatment/control of pruritus associated with allergic dermatitis and treatment/control of clinical manifestations of atopic dermatitis in dogs at least 12 months of age. To evaluate the effectiveness of oclacitinib in dogs with flea allergy dermatitis, the JAK1 selective inhibitor was tested in a placebo-controlled, masked, single-dose (0.4 mg/kg) or repeat-dose (0.4 mg/kg, twice daily for 2 weeks) study. Pruritic behaviors were quantitated by video recording, and erythema and skin lesions were assessed using a 10-cm visual analog scale (VAS). Results showed that oclacitinib reduced pruritus by 61% as early as 1.5 h after a single oral dose compared to placebo, with an average reduction (compared to placebo) of 85% 1–5 h after dosing (0.4 mg/kg; p < .0001). Oclacitinib also significantly reduced erythema (p < .0001) and skin lesion (p < .0005) VAS scores on Day 14 compared to placebo in a repeat dose study. No adverse events were noted during the conduct of these studies. IL-31 concentrations were elevated in the majority of dogs after flea infestation, suggesting JAK1-dependent cytokines may drive clinical signs of flea allergy dermatitis. These findings show that oclacitinib, an inhibitor of JAK1-dependent cytokines involved in allergy and inflammation can rapidly reduce clinical signs associated with flea allergic dermatitis in dogs.

奥克替尼是一种新型 Janus 激酶 (JAK) 抑制剂,能有效抑制参与过敏、炎症和瘙痒的 JAK1 依赖性细胞因子(IL-2、IL-4、IL-6、IL-13 和 IL-31)。奥克替尼(Apoquel®,Zoetis Inc,Parsippany,NJ)被批准用于治疗/控制与过敏性皮炎相关的瘙痒症,以及治疗/控制 12 个月以上犬只特应性皮炎的临床表现。为了评估奥克替尼对跳蚤过敏性皮炎犬的疗效,在一项安慰剂对照、掩蔽、单剂量(0.4 毫克/千克)或重复剂量(0.4 毫克/千克,每天两次,连续两周)研究中对这种 JAK1 选择性抑制剂进行了测试。瘙痒行为通过视频记录进行量化,红斑和皮损通过 10 厘米视觉模拟量表(VAS)进行评估。结果显示,与安慰剂相比,奥卡替尼早在单次口服后1.5小时就能减少61%的瘙痒,用药后1-5小时平均减少85%(与安慰剂相比)(0.4 mg/kg; p
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引用次数: 0
Is it time to stop teaching pharmacology and focus on treatment planning instead? 是时候停止药理学教学,转而关注治疗计划了吗?
IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-24 DOI: 10.1111/jvp.13467
Martin Hawes, Virginia Fajt, Arno Werners
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引用次数: 0
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Journal of veterinary pharmacology and therapeutics
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