Disposition kinetics and tissue residues of tilmicosin following intravenous, subcutaneous, single and multiple oral dosing in geese (Anser anser domesticus)

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-06-07 DOI:10.1111/jvp.13461
Krzysztof Bourdo, Charbel Fadel, Mario Giorgi, Andrejs Šitovs, Amnart Poapolathep, Beata Łebkowska-Wieruszewska
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Abstract

Tilmicosin (TMC), a semi-synthetic macrolide antibiotic, is widely used in veterinary medicine due to its broad-spectrum, bacteriostatic properties. Frequently administered in various birds species, it is likely used off-label in geese as well. The study sought to investigate TMC's pharmacokinetics, tissue residues, in geese through in vivo experiments. The study involved longitudinal open studies on 15 healthy adult males, with three phases separated by one-month washout periods. Geese were administered TMC through intravenous (IV, 5 mg/kg), subcutaneous (SC, 10 mg/kg), and oral (PO, 25 mg/kg for five consecutive days) routes, with blood samples drawn at specific intervals. Tissue samples were also collected for subsequent analysis at pre-assigned times. TMC in goose plasma was quantified by a fully validated HPLC method. Plasma concentrations were quantified up to 4 hr for the PO and IV routes, and up to 10 hr in the SC route. Significant variations in bioavailability were observed between SC (87%) and PO (4%) routes. The body extraction ratio was low at 0.03, suggesting minimal ability of the liver and kidneys to eliminate TMC. Multiple oral doses showed no plasma accumulation, but tissue data revealed extensive distribution and prolonged residence, up to 120 h, suggesting a sustained therapeutic effect despite the brief plasma half-life. Regarding the multiple PO doses, provisional withdrawal times of 6, 7.5, and 8 days were suggested for the liver, muscles, and kidneys, respectively, according to the MRL set for these matrices in chickens by EMA. In conclusion, while the practical oral administration is discouraged at the population level, SC administration of TMC may be appropriate for geese, albeit impractical for flock therapy.

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鹅(Anser anser domesticus)静脉注射、皮下注射、单次口服和多次口服替米考星后的处置动力学和组织残留。
替米考星(TMC)是一种半合成的大环内酯类抗生素,因其广谱、抑菌的特性而被广泛应用于兽医领域。它经常被用于各种鸟类,也可能被用于鹅的非标示治疗。该研究试图通过体内实验来调查 TMC 在鹅体内的药代动力学和组织残留。该研究对 15 只健康的成年雄鹅进行了纵向开放式研究,分为三个阶段,每阶段之间有一个月的冲洗期。研究人员通过静脉注射(静脉注射,每公斤 5 毫克)、皮下注射(皮下注射,每公斤 10 毫克)和口服(口服,每公斤 25 毫克,连续五天)途径给鹅服用 TMC,并在特定时间间隔抽取血液样本。此外,还在预先指定的时间采集组织样本进行后续分析。鹅血浆中的 TMC 采用经过全面验证的高效液相色谱法进行定量。通过口服和静脉注射途径对血浆浓度进行定量分析的时间长达 4 小时,通过静脉注射途径对血浆浓度进行定量分析的时间长达 10 小时。经皮下注射(87%)和口服(4%)两种途径的生物利用度差异显著。体内萃取率很低,仅为 0.03,这表明肝脏和肾脏消除 TMC 的能力极低。多剂量口服显示没有血浆蓄积,但组织数据显示其分布广泛,停留时间长达 120 小时,表明尽管血浆半衰期很短,但仍有持续的治疗效果。关于多次口服剂量,根据 EMA 为鸡体内这些基质设定的最高残留限量,建议肝脏、肌肉和肾脏的暂定停药时间分别为 6 天、7.5 天和 8 天。总之,虽然不鼓励在人群中实际口服 TMC,但对鹅来说,体表注射 TMC 可能是合适的,尽管在鹅群中进行治疗并不实际。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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