Metronidazole pharmacokinetics in geese (Anser anser domesticus) after intravenous and oral administrations

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2023-11-30 DOI:10.1111/jvp.13421
Charbel Fadel, Beata Łebkowska-Wieruszewska, Krzysztof Bourdo, Amnart Poapolathep, Georges Hassoun, Mario Giorgi
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Abstract

Metronidazole (MTZ) is a 5-nitroimidazole anti-bacterial and anti-protozoal drug. In human and companion animal medicine, MTZ remains widely used due to its effectiveness against anaerobic bacteria and protozoa. In farm animals, however, MTZ is currently prohibited in several countries due to insufficient data on nitroimidazoles. The purpose of this study was to assess its pharmacokinetics (PK) in geese after single intravenous (IV) and oral (PO) administrations. Fifteen-month old healthy male geese (n = 8) were used. Geese were subjected to a two-phase, single-dose (10 mg/kg IV, 50 mg/kg PO), open, longitudinal study design with a two-week washout period between the IV and PO phases. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma MTZ concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software with a non-compartmental approach. MTZ was still quantifiable and well above the LLOQ at 24 h after both routes of administration. Following IV administration, terminal elimination half-life, volume of distribution, and total clearance were 5.47 h, 767 mL/kg, and 96 mL/h/kg, respectively. For the PO route, the bioavailability was high (85%), and the mean peak plasma concentration was 60.27 μg/mL at 1 h. When parameters were normalized for the dose, there were no statistically significant differences for any of the PK parameters between the two routes of administration. The study shows that oral administration of MTZ seems to be promising in geese, although comprehensive research on its pharmacodynamics and multiple-dose studies are necessary before its adoption in geese can be further considered.

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静脉和口服给药甲硝唑在鹅体内的药代动力学。
甲硝唑(Metronidazole, MTZ)是一种5-硝基咪唑类抗菌抗原虫药物。在人类和伴侣动物医学中,由于其对厌氧细菌和原生动物的有效性,MTZ仍然被广泛使用。然而,由于关于硝基咪唑的数据不足,目前在一些国家禁止在农场动物中使用MTZ。本研究的目的是评估单次静脉(IV)和口服(PO)给药后其在鹅体内的药代动力学(PK)。选用15月龄健康公鹅8只。鹅采用两期单剂量(10 mg/kg静脉注射,50 mg/kg PO)开放纵向研究设计,IV期和PO期之间有两周的洗脱期。分别于0、0.085(仅静脉)、0.25、0.5、0.75、1、1.5、2、4、6、8、10、24和48 h从左侧静脉抽血至肝素化管。血浆MTZ浓度采用HPLC耦合UV检测器进行测量,数据采用PKanalix™软件进行非区室方法的药代动力学分析。两种给药途径24小时后,MTZ仍可量化,且远高于LLOQ。静脉给药后,终末消除半衰期、分布体积和总清除率分别为5.47 h、767 mL/kg和96 mL/h/kg。PO途径生物利用度高(85%),1 h血药浓度平均峰值为60.27 μg/mL。当剂量参数归一化后,两种给药途径之间的任何PK参数均无统计学差异。研究表明,口服MTZ在鹅中似乎很有前景,但在进一步考虑其在鹅中的应用之前,需要对其药效学和多剂量研究进行全面研究。
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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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