Laboratory of Veterinary Drug Development and Evaluation, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471023, China.
Laboratory of Veterinary Drug Development and Evaluation, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, 471023, China.
Poult Sci. 2024 Oct;103(10):104168. doi: 10.1016/j.psj.2024.104168. Epub 2024 Aug 2.
This experiment aimed to investigate the in vitro antimicrobial activity of danofloxacin against Escherichia coli (E. coli) isolated from pigeons, as well as the pharmacokinetics of danofloxacin in pigeons following oral (PO), intramuscular (IM), and intravenous (IV) administration. The minimum inhibitory concentration (MIC) of danofloxacin was first determined for 38 clinical E. coli strains using the micro broth dilution method. Subsequently, 30 healthy pigeons were weighed and randomly divided into 3 groups: IM, IV, and PO, with 10 pigeons in each group. Danofloxacin was given at 5 mg/kg body weight (BW) through 3 different routes. Blood was collected, and plasma was separated at various time points from 0 to 48 h. Plasma samples were analyzed for danofloxacin concentrations using a validated HPLC method. Pharmacokinetic analysis was performed using Phoenix software and a noncompartmental analytical (NCA) method. The results indicated that danofloxacin had a strong antibacterial effect on E. coli, with a MIC of 0.5 μg/mL. The noncompartmental analysis showed that after PO and IM administration at 5 mg/kg in pigeons, peak plasma concentrations (C) of 0.61 and 1.62 μg/mL were reached at 4.5 and 0.53 h, respectively. The oral and intramuscular bioavailability (F) were 68.08% ± 24.82% and 87.82% ± 25.36%, respectively. Following IV administration, danofloxacin was widely distributed in pigeons, with volume of distribution (V) and volume of distribution at steady state (V) values of 6.11 ± 2.01 and 4.65 ± 1.62 L/kg, respectively, and was eliminated slowly, with an elimination half-life (t) of 6.41 ± 2.15 h. Based on the calculated ratio values of AUC/MIC, the current IV, IM, and PO doses of 5 mg/kg of danofloxacin would be expected to effectively treat pigeons infected with E. coli strains with MIC values equal to or less than 0.5 μg/mL.
本实验旨在研究丹氟沙星对鸽子源大肠杆菌(E. coli)的体外抗菌活性,以及鸽子经口服(PO)、肌肉注射(IM)和静脉注射(IV)给予丹氟沙星后的药代动力学。首先采用微量肉汤稀释法测定 38 株临床分离大肠杆菌的最小抑菌浓度(MIC)。随后,将 30 只健康鸽子称重并随机分为 3 组:IM、IV 和 PO,每组 10 只。鸽子以 5mg/kg 体重(BW)经 3 种不同途径给予丹氟沙星。在 0 至 48 小时的不同时间点采集血液并分离血浆。采用经验证的 HPLC 法分析血浆样品中的丹氟沙星浓度。使用 Phoenix 软件和非房室分析(NCA)方法进行药代动力学分析。结果表明,丹氟沙星对大肠杆菌具有很强的抗菌作用,MIC 为 0.5μg/mL。非房室分析显示,鸽子经 PO 和 IM 给予 5mg/kg 丹氟沙星后,分别在 4.5 和 0.53 小时达到血浆峰浓度(C)0.61 和 1.62μg/mL。口服和肌肉注射生物利用度(F)分别为 68.08%±24.82%和 87.82%±25.36%。IV 给予丹氟沙星后,其在鸽子体内广泛分布,分布容积(V)和稳态分布容积(V)值分别为 6.11±2.01 和 4.65±1.62L/kg,消除缓慢,消除半衰期(t)为 6.41±2.15h。基于 AUC/MIC 的计算比值,当前 IV、IM 和 PO 剂量为 5mg/kg 的丹氟沙星有望有效治疗 MIC 值等于或小于 0.5μg/mL 的大肠杆菌感染鸽子。