Sartini Irene, Łebkowska-Wieruszewska Beata, Lisowski Andrzej, Poapolathep Amnart, Giorgi Mario
Department of Veterinary Medicine, University of Sassari, Sassari, Italy.
Institute of Pharmacology, Toxicology and Environmental Protection, University of Life Sciences, Lublin, Poland.
Res Vet Sci. 2021 May;136:11-17. doi: 10.1016/j.rvsc.2021.01.017. Epub 2021 Jan 28.
Danofloxacin is a fluoroquinolone developed for veterinary medicine and used in avian species for the treatment of numerous bacterial infections. However, no pharmacokinetic data have been reported in geese. The aim of the study was three-fold: (i) to evaluate the pharmacokinetics of danofloxacin in geese after single oral (PO) and intravenous (IV) administrations; (ii) to define its residue depletion profile in different goose tissues, and (iii) to recreate a multiple-dose simulation in the practical context of large-scale breeding. Twenty-four healthy geese were randomly divided in three groups each composed of eight animals. Group 1 received danofloxacin IV (5 mg/kg) and groups 2 and 3 were treated PO with the same dose. Blood was collected until 24 h (IV; group 1) and 48 h (PO; group 2) after administration. Two animals from group 3 were sacrificed at 6, 10, 24 and 48 h to collect samples of muscle, heart, kidney, liver, and lung. Danofloxacin was quantified in each matrix using a validated high-performance liquid chromatography method with spectrofluorimetric detection and the pharmacokinetic analysis was performed using non-compartmental and compartmental approaches. Danofloxacin showed a moderate elimination half-life (6.61 h), a slow clearance (0.35 mL/g*h) and a large volume of distribution (1.46 mL/g). The peak plasma concentration after PO administration and the time to reach it were 0.96 μg/mL and 1.70 h, respectively. The oral bioavailability was moderate (58%). Higher residue concentration was found in liver and kidney, compared to the other tissues. If the AUC value found in the present study is included in the pharmacokinetic/pharmacodynamic index (AUC/MIC) for the prediction of fluoroquinolones' efficacy, danofloxacin seems to be effective in geese against gram-negative bacteria with a minimum inhibitory concentration (MIC) < 0.076 μg/mL and against S. pneumoniae with a MIC < 0.29 μg/mL after a single PO dose of 5 mg/kg. Liver and kidney showed the highest drug tissue penetration value, with an explorative withdrawal time of 2.6 and 3.8 days, respectively. A practical multiple-dose regimen simulation does not lead to significant plasma drug accumulation.
达氟沙星是一种为兽医学开发的氟喹诺酮类药物，用于禽类治疗多种细菌感染。然而，尚未有关于鹅的药代动力学数据报道。本研究的目的有三个：（i）评估达氟沙星在鹅单次口服（PO）和静脉注射（IV）给药后的药代动力学；（ii）确定其在不同鹅组织中的残留消除情况，以及（iii）在大规模养殖的实际情况下进行多剂量模拟。24只健康鹅随机分为三组，每组8只。第1组接受达氟沙星静脉注射（5mg/kg），第2组和第3组接受相同剂量的口服给药。给药后分别在24小时（静脉注射；第1组）和48小时（口服；第2组）采集血液。第3组的两只动物在6、10、24和48小时处宰杀，采集肌肉、心脏、肾脏、肝脏和肺的样本。使用经过验证的高效液相色谱法结合荧光检测对各基质中的达氟沙星进行定量，并使用非房室和房室方法进行药代动力学分析。达氟沙星显示出中等的消除半衰期（6.61小时）、缓慢的清除率（0.35mL/g*h）和较大的分布容积（1.46mL/g）。口服给药后的血浆峰值浓度和达到峰值的时间分别为0.96μg/mL和1.70小时。口服生物利用度中等（58%）。与其他组织相比，肝脏和肾脏中的残留浓度更高。如果将本研究中发现的AUC值纳入预测氟喹诺酮类药物疗效的药代动力学/药效学指数（AUC/MIC）中，单次口服5mg/kg剂量后，达氟沙星似乎对最低抑菌浓度（MIC）<0.076μg/mL的革兰氏阴性菌以及MIC<0.29μg/mL的肺炎链球菌在鹅体内有效。肝脏和肾脏显示出最高的药物组织渗透值，探索性停药时间分别为2.6天和3.8天。实际的多剂量方案模拟不会导致血浆药物显著蓄积。
