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Intravenous Ampicillin/Sulbactam in Critically Ill Dogs has Variable Pharmacokinetics 危重犬静脉注射氨苄西林/舒巴坦具有可变药代动力学。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-13 DOI: 10.1111/jvp.70004
Robert Goggs, Sarah Robbins, Julie Menard, Jamie Selman, Jeff Beverly, Sydney Kraus-Malett, Mark G. Papich

Achieving therapeutic plasma concentrations is essential for effective antimicrobial drug (AMD) treatment. Critical illness alters drug distribution and clearance, potentially impacting AMD effectiveness. We conducted a prospective observational study in 25 critically ill dogs to evaluate the pharmacokinetics (PK) of intravenous (IV) ampicillin/sulbactam and achievement of the efficacy target of ≥ 50% of the dosing interval with unbound plasma drug concentrations above the minimum inhibitory concentration (fT > MIC). All dogs received IV ampicillin/sulbactam from a commercial formulation at a dosage of 20 mg/kg ampicillin/10 mg/kg sulbactam. Plasma concentrations were measured using liquid chromatography–mass spectrometry. PK modeling determined best-fit compartmental models, and Monte Carlo simulations evaluated the probability of target attainment for bacterial MICs. A one-compartment model best described ampicillin PK, while a two-compartment model fit sulbactam. Monte Carlo simulations indicated a 90% probability that ampicillin at 20 mg/kg IV q8 h would achieve the Clinical and Laboratory Standards Institute (CLSI) veterinary breakpoint of 0.25 μg/mL for > 50% of the dosing interval. There was only a 10% probability of achieving the human breakpoint of 8 μg/mL. At 0.25 μg/mL, most Enterobacterales isolates would be resistant. The ampicillin/sulbactam dosage tested meets veterinary CLSI standards for ampicillin but might not effectively treat Enterobacterales infections in critically ill dogs.

达到治疗性血浆浓度是有效治疗抗微生物药物(AMD)的必要条件。危重疾病改变了药物分布和清除,潜在地影响了AMD的有效性。我们对25只危重犬进行了前瞻性观察研究,以评估静脉注射氨苄西林/舒巴坦的药代动力学(PK),以及在非结合血浆药物浓度高于最低抑制浓度(fT > MIC)的情况下,达到≥50%的给药间隔的疗效目标。所有的狗都接受了商业配方的氨苄西林/舒巴坦静脉注射,剂量为20mg /kg氨苄西林/ 10mg /kg舒巴坦。采用液相色谱-质谱法测定血浆浓度。PK模型确定了最适合的区室模型,蒙特卡罗模拟评估了细菌mic达到目标的概率。单室模型最适合氨苄西林PK,而双室模型适合舒巴坦。蒙特卡罗模拟表明,氨苄西林20mg /kg IV q8 h有90%的可能性达到临床和实验室标准协会(CLSI)兽医临界点0.25 μg/mL,给药间隔为50%。只有10%的概率达到8 μg/mL的人体断点。在0.25 μg/mL浓度下,大多数肠杆菌菌株具有耐药性。测试的氨苄西林/舒巴坦剂量符合氨苄西林兽医CLSI标准,但可能无法有效治疗危重犬的肠杆菌感染。
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引用次数: 0
Pharmacokinetics of Single Dose and Multidose Oral Gabapentin in Goats (Capra aegagrus hircus) 单剂量和多剂量口服加巴喷丁在山羊体内的药动学。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-12 DOI: 10.1111/jvp.70006
Jessie C. Ziegler, Meera Heller, Sherry Cox, Joe S. Smith

There is a shifting public perception of animal welfare that has increased demand for establishing pain management strategies in livestock. Gabapentin is often utilized in practice to mitigate neuropathic pain. However, there is little pharmacokinetic information to guide its use in goats. The objectives of this study were to describe the pharmacokinetics of oral gabapentin in goats given as a single dose (SD) and multidose (MD) regimen, as well as to document any adverse effects after administration. Six healthy adult goats were administered 15 mg/kg of gabapentin orally once for the SD trial, and every 12 h for 6 doses for the MD trial. Plasma samples were collected and analyzed via reversed-phase high-performance liquid chromatography. After SD administration, maximum plasma concentration, time to maximum concentration, and elimination half-life were: 3.22 μg/mL; 4.49 h; and 8.15 h, respectively. After MD administration, maximum plasma concentration and time to maximum concentration were: 4.56 μg/mL and 2.24 h. Accumulation ratio (R) was 1.66 ± 0.81 when comparing the MD AUC12h to the SD AUC12h. Clinicians should be aware of the potential for increased accumulation ratio with multiple dosing strategies.

公众对动物福利的看法正在发生变化,这增加了建立牲畜疼痛管理策略的需求。加巴喷丁在实践中经常用于减轻神经性疼痛。然而,很少有药代动力学信息来指导其在山羊中的使用。本研究的目的是描述口服加巴喷丁单剂量(SD)和多剂量(MD)方案在山羊体内的药代动力学,并记录给药后的任何不良反应。6只健康成年山羊在SD试验中口服加巴喷丁15 mg/kg,在MD试验中每12 h口服6次。血浆样品采集并通过反相高效液相色谱分析。SD给药后,最大血药浓度、达到最大浓度所需时间、消除半衰期分别为:3.22 μg/mL;4.49 h;分别是8.15小时。给药后最大血药浓度为4.56 μg/mL,达到最大血药浓度所需时间为2.24 h。MD AUC12h与SD AUC12h的积累比(R)为1.66±0.81。临床医生应该意识到多种给药策略可能增加积累比。
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引用次数: 0
Effect of Gender on the Pharmacokinetics of Meloxicam in Sheep 性别对美洛昔康在绵羊体内药代动力学的影响。
IF 1.7 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2025-06-06 DOI: 10.1111/jvp.70005
Orhan Corum, Kamil Uney, Duygu Durna Corum, Devran Coskun, Fatma Akin, Halis Oguz, Muammer Elmas

The objective of this investigation was to ascertain the impact of gender on the pharmacokinetics of meloxicam in sheep. The research was carried out on six female and six male Romanov sheep. Meloxicam was administered intravenously to sheep at a dose of 1 mg/kg. To determine the change in meloxicam concentration with time, blood samples were collected at 17 different time points up to 120 h after administration. Meloxicam concentrations in plasma samples were determined using high-performance liquid chromatography. The pharmacokinetics of meloxicam in sheep was found to differ according to gender. The values of total clearance (ClT), volume of distribution at steady state (Vdss), and elimination half-life (t1/2λz) of meloxicam in female sheep were 4.51 ± 0.56 mL/h/kg, 69.18 ± 6.68 mL/kg, and 11.96 ± 0.33 h, respectively. Compared to female sheep, ClT and Vdss were increased, and t1/2λz was decreased in male sheep. Plasma concentration and area under the curve of meloxicam were higher in female sheep. The findings of this study indicate that meloxicam's pharmacokinetics are not uniform across genders in Romanov sheep, with notable variations in plasma concentration, clearance, and half-life. These variations emphasize the importance of considering gender in the pharmacotherapy of sheep, potentially guiding clinicians in adjusting dosages for optimal therapeutic outcomes and maintaining food safety standards.

本研究的目的是确定性别对美洛昔康在绵羊体内药代动力学的影响。研究对象为6只雌性和6只雄性罗曼诺夫羊。以1 mg/kg的剂量静脉滴注美洛昔康给羊。为了确定美洛昔康浓度随时间的变化,在给药后120 h的17个不同时间点采集血样。采用高效液相色谱法测定血浆样品中的美洛昔康浓度。发现美洛昔康在绵羊体内的药代动力学因性别而异。美洛昔康在母羊体内的总清除率(ClT)、稳态分布体积(Vdss)和消除半衰期(t1/2λz)分别为4.51±0.56 mL/h/kg、69.18±6.68 mL/kg和11.96±0.33 h。与母羊相比,母羊ClT和Vdss升高,t1/2λz降低。雌羊的美洛昔康血药浓度和曲线下面积较高。本研究结果表明,在罗曼诺夫羊中,美洛昔康的药代动力学在不同性别之间并不均匀,在血浆浓度、清除率和半衰期方面存在显著差异。这些差异强调了在绵羊药物治疗中考虑性别的重要性,可能指导临床医生调整剂量以获得最佳治疗效果并保持食品安全标准。
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引用次数: 0
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
期刊
Journal of veterinary pharmacology and therapeutics
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