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猪静脉注射和口服阿莫西林-克拉维酸颗粒组合后的生物利用度和药代动力学。

The bioavailability and pharmacokinetics of an amoxicillin-clavulanic acid granular combination after intravenous and oral administration in swine.

机构信息

Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, China.

Laboratory of Quality & Safety Risk Assessment for Animal Products on Chemical Hazards (Beijing), Ministry of Agriculture and Rural Affairs of the People's Republic of China, Beijing, China.

出版信息

J Vet Pharmacol Ther. 2021 Jan;44(1):126-130. doi: 10.1111/jvp.12916. Epub 2020 Oct 15.

DOI:10.1111/jvp.12916
PMID:33063331
Abstract

The pharmacokinetic behaviours of amoxicillin (AMX) and clavulanic acid (CA) in swine were studied after either an intravenous or oral administration of AMX (10 mg/kg) and CA (2.5 mg/kg). The concentrations of these two medicines in swine plasma were determined using high-performance liquid chromatographic-tandem mass spectrometry, and the data were analysed using a noncompartmental model with the WinNonlin software. After intravenous administration, both substances were absorbed rapidly and reached their effective therapeutic concentration quickly. CA was eliminated more slowly compared with AMX. Moreover, the distribution volume of AMX was larger than that of CA, suggesting that AMX could penetrate tissues better. After oral administration of the granular formulation, no significant difference was observed in the mean elimination half-life value between AMX and CA. The mean maximal plasma concentrations of AMX and CA, reached after 1.14 and 1.32 hr, were 2.58 and 1.91 μg/m, respectively. The mean oral bioavailability of AMX and CA was 23.6% and 26.4%, respectively. After oral administration, the T>MIC for three common respiratory pathogens was over 6.12 hr. Therefore, oral administration could be more effective in the clinical therapy of pigs, especially when administered twice daily.

摘要

阿莫西林(AMX)和克拉维酸(CA)在猪体内的药代动力学行为研究分别在静脉注射或口服 AMX(10mg/kg)和 CA(2.5mg/kg)后进行。采用高效液相色谱-串联质谱法测定猪血浆中这两种药物的浓度,用非房室模型和 WinNonlin 软件分析数据。静脉注射后,两种物质均迅速吸收,迅速达到有效治疗浓度。CA 的消除速度比 AMX 慢。此外,AMX 的分布容积大于 CA,提示 AMX 能更好地穿透组织。口服颗粒制剂后,AMX 和 CA 的平均消除半衰期值无显著差异。AMX 和 CA 的平均最大血浆浓度分别在 1.14 和 1.32 小时后达到,分别为 2.58 和 1.91μg/ml。AMX 和 CA 的平均口服生物利用度分别为 23.6%和 26.4%。口服后,三种常见呼吸道病原体的 T>MIC 超过 6.12 小时。因此,口服给药在猪的临床治疗中可能更有效,尤其是每日给药两次时。

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