ABSTRACT

1. The aim of this study was to assess the pharmacokinetics of levofloxacin, a third-generation fluoro-quinolone antimicrobial drug, in geese (n = 26) after either single intravenous or oral administration, and to evaluate the depletion profile in goose muscle, heart, liver, kidney and lung after a single oral dose.

2. The pharmacokinetic study involved 16 geese which were randomly divided into two groups (n = 8/group), the first received levofloxacin (2 mg/kg) intravenously while the second was treated with orally (5 mg/kg). The tissue depletion study involved 10 geese which were dosed orally (5 mg/kg) and two animals were killed at different time-points in order to collect the selected tissues. Levofloxacin was quantified in all the matrices tested by a validated high-performance liquid chromatography (HPLC) method, using a spectrofluorimetric detector. The pharmacokinetics were analysed using a non-compartmental model.

3. Plasma concentrations were quantified after up to 24 h in animals administered intravenously and up to 48 h after oral treatment. Levofloxacin was rapidly absorbed after oral administration (T_max = 0.38 h) showing high bioavailability (95.57 ± 20.61%). The drug showed a moderate volume of distribution (1.40 ± 0.28 ml/g) and rapid clearance (0.28 ± 0.06 ml/g/h). No statistical differences in estimates were found between the two different administration methods (P > 0.05). Drug residues were highest at 6 h and decreased constantly up to 48 h in all the selected tissues. Liver and kidney had the highest levofloxacin concentrations.

4. According to the pharmacokinetic/pharmacodynamic surrogate index (AUC/MIC) the levofloxacin dose regimen (after oral administration) used in the present study could be active against bacteria at a minimum inhibitory concentration (MIC) > 0.24 μg/ml in geese. In addition, drug accumulation in the liver might be controlled using an estimated preliminary withdrawal time of 90 h.

摘要

1. 本研究的目的是评估左氧氟沙星（一种第三代氟喹诺酮类抗菌药物）在鹅（n = 26）中单次静脉内或口服给药后的药代动力学，并评估鹅肌肉中的消耗曲线，单次口服后的心脏、肝脏、肾脏和肺脏。

2.药代动力学研究涉及16只鹅，随机分为两组（n = 8/组），第一组静脉注射左氧氟沙星（2 mg/kg），第二组口服（5 mg/kg）。组织耗竭研究涉及 10 只鹅，它们被口服给药 (5 mg/kg)，并在不同的时间点杀死两只动物以收集选定的组织。使用荧光分光检测器，通过经过验证的高效液相色谱 (HPLC) 方法对所有测试的基质中的左氧氟沙星进行量化。使用非房室模型分析药代动力学。

3. 静脉内给药最多 24 小时后和口服治疗最多 48 小时后，对血浆浓度进行量化。左氧氟沙星口服后吸收迅速（T _max  = 0.38 h），生物利用度高（95.57 ± 20.61%）。该药物表现出中等分布容积（1.40 ± 0.28 ml/g）和快速清除（0.28 ± 0.06 ml/g/h）。两种不同的给药方法之间的估计值没有统计学差异（P > 0.05）。在所有选定的组织中，药物残留在 6 小时最高，并持续下降至 48 小时。肝脏和肾脏的左氧氟沙星浓度最高。

4. 根据药代动力学/药效学替代指数（AUC/MIC），本研究中使用的左氧氟沙星给药方案（口服后）在最低抑菌浓度（MIC）>0.24 μg/ml的鹅中对细菌具有活性。此外，估计的初步停药时间为 90 小时，可以控制肝脏中的药物积累。